Interleukin-10 Gene Research Articles

Biomimetic non-collagenous proteins-calcium phosphate complex with superior osteogenesis via regulating macrophage IL-27 secretion

Traumatic defects or non-union fractures presents a substantial challenge in the fields of tissue engineering and regenerative medicine. Although synthetic calcium phosphate-based biomaterials (CaPs) such as dibasic calcium phosphate anhydrate (DCPA) are commonly employed for bone repair, their inadequate cellular immune responses significantly impede sustained degradation and optimal osteogenesis. In this study, drawing inspiration from the key structure of an acidic non-collagenous protein-CaP complex (ANCPs-CaP) essential for natural bone formation, we prepared biomimetic mineralized dibasic calcium phosphate (MDCPA). This preparation utilized plant-derived non-collagenous protein Zein as the organic template and acidic artificial saliva as the mineralization medium. Physicochemical property analysis revealed that MDCPA is a complex of Zein and DCPA, which mimics the composite of the natural ANCP-CaP. Moreover, MDCPA exhibited enhanced biodegradability and osteogenic potential. Mechanistic insight revealed that MDCPA can be phagocytized and degraded by macrophages via the FCγRIII receptor, leading to the release of interleukin 27 (IL-27), which promotes osteogenic differentiation by osteoimmunomodulation. The critical role of IL-27 in osteogenesis is further confirmed using IL-27 gene knockout mice. Additionally, MDCPA demonstrates effective healing of critical-sized defects in rat cranial bones within only 4 w, providing a promising basis and valuable insights for critical-sized bone defects regeneration.

In Situ Expression of Yak IL-22 in Mammary Glands as a Treatment for Bovine Staphylococcus aureus-Induced Mastitis in Mice.

Since the development of dairy farming, bovine mastitis has been a problem plaguing the whole industry, which has led to a decrease in milk production, a reduction in dairy product quality, and an increase in costs. The use of antibiotics to treat mastitis can cause a series of problems, which can bring a series of harm to the animal itself, such as the development of bacterial resistance and dramatic changes in the gut flora. However, the in vivo and in vitro antibacterial activity of yak Interleukin-22 (IL-22) and its application in mastitis caused by Staphylococcus aureus have not been reported. In this study, the mammary gland-specific expression plasmid pLF-IL22 of the yak IL-22 gene was constructed and expressed in MAC-T cells and mammary tissue of postpartum female mice. The coding region of the IL-22 gene in yaks is 573 bp, which can encode 190 amino acids, and the homology difference in the IL-22 gene in yaks is less than 30%, which indicates certain conservation. IL-22 is a hydrophilic protein with a total positive charge of four, the presence of a signal peptide, and the absence of a transmembrane domain. Sufficient expression of IL-22 effectively inhibited the high expression of inflammatory factors caused by Staphylococcus aureus, reduced the symptoms of mammary gland histopathology, and alleviated mastitis. Under the action of IL-22, the intestinal flora of mastitis mice also changed, the abundance of intestinal Bacilli, Prevotellaceae, and Alloprevotella in mice increased after treatment, and the pathogenic bacteria decreased. These findings provide new insights into the potential application of the yak IL-22 gene in the treatment of bovine mastitis in the future.

Allelic, Genotypic, and Haplotypic Analysis of Cytokine IL17A, IL17F, and Toll-like Receptor TLR4 Gene Polymorphisms in Metabolic-Dysfunction-Associated Steatotic Liver Disease: Insights from an Exploratory Study.

(1) Background: Interleukin 17 (IL17) and toll-like receptor 4 (TLR4) elevate the risk of metabolic and liver diseases. (2) Methods: This study's objective was to explore the association of IL17 and TLR4 gene polymorphisms with MASLD susceptibility and test their effect on serum IL17 and TLR4 levels. A total of 43 patients with MASLD (MASH/MAFL) and 38 healthy individuals were genotyped for IL17F-A7488G, IL17A-G197A, TLR4-Asp299Gly, and TLR4-Thr399Ile polymorphisms using PCR-RFLP. ELISA methods determined IL17F, IL17A, and TLR4 serum levels. (3) Conclusions: Patients carrying the variant genotypes (A/G + G/G) of IL17-A7448G (OR = 5.25), (G/A + A/A) of IL17-G197A (OR = 10.57), (Asp/Gly + Gly/Gly) of TLR4-Asp299Gly (OR = 3.52), or (Thr/Ile + Ile/Ile) of TLR4-Thr399Ile (OR = 9.87) had significantly increased odds of MASH. Genotype (G/A + A/A) of IL17-G197A was significantly associated with the odds of MAFL (p = 0.0166). Allele A of the IL17-G197A polymorphism was significantly related to increased odds of MAFL (OR = 4.13, p = 0.0133). In contrast, allele A of IL17-G197A (OR = 5.41, p = 0.008), allele Gly of TLR4-Asp299Gly (OR = 3.19, p = 0.046), and allele Ile of TLR4-Thr399Ile (OR = 6.94, p = 0.008) polymorphisms were significantly related to an increased risk of MASH. Allele A of IL17A-G197A, allele Gly of TLR4-Asp299Gly, and allele Ile of TLR4-Thr399Ile gene polymorphisms were significantly associated with the increased odds of MASLD. In patients with MASLD, we found significant influence from the IL17A-G197A gene polymorphism on IL17F levels (p = 0.0343).

Effect of Dietary Benzoic Acid and Oregano Essential Oil as a Substitute for an Anti-Coccidial Agent on Growth Performance and Physiological and Immunological Responses in Broiler Chickens Challenged with Eimeria Species.

To overcome the antimicrobial residues in food, benzoic acid (BA) and oregano essential oil (OEO) are used in the broiler chicken industry. Independently, both exerted anticoccidial and antimicrobial actions and improved growth performance in broiler chickens. Their effect may be multiplied when they are used in combination. This present study was carried out to evaluate the efficacy of dietary BA and OEO alone or in combination as a substitute for a commercial coccidiostatic drug on growth performance and physiological and immunological responses in broiler chickens challenged with Eimeria species. A total of 252 unsexed 1-day-old broiler chicks were equally allotted to 36 pens, each pen containing seven chicks. The pens were randomly assigned to six treatments with six pens (replicates) for each treatment (n = 6)-(i) negative control, (ii) positive control, coccidia-challenged and non-treated, (iii) supplemented with salinomycin (an anti-coccidial drug) at 60 mg/kg of feed and coccidia-challenged, (iv) supplemented with BA at 500 mg/kg of feed and coccidia-challenged, (v) supplemented with OEOat 500 mg/kg of feed and coccidia-challenged (OEO), and (vi) supplemented with BA at 500 mg/kg of feed and OEO at 500 mg/kg of feed and coccidia-challenged (B&O). The liver enzymes and thyroxine and creatinine levels were not affected (p > 0.05) both in coccidia-challenged and supplemented chickens. The BA and OEO applied separately or in combination (B&O) significantly (p < 0.05) reduced gut pathogenic bacteria (Salmonella and Escherichia coli) and Eimeria spp., and concurrently enhanced (p > 0.05) the Lactobacillus population with better body weight gain, improved feed utilization, and superior hematological values. It also up-regulated (p > 0.05) the interferon-γ gene expression and down-regulated (p < 0.05) the interleukin-10 and Toll-like receptor-4 gene expression to protect the chickens from inflammatory reactions, which were not demonstrated in salinomycin-treated birds. The B&O supplementation increased (p < 0.05) the immune system by enhancing Eimeria-specific immunoglobulin Y titer and lymphocyte proliferation response. This study suggests that the combined application of OEO and BA can substitute for a commercial anti-coccidial agent (salinomycin) in controlling coccidiosis as well as improving growth performance, gut health, and immune responses in broiler chickens with a means of antimicrobial-resistant free food products.

Evaluation of angiotensin converting enzyme insertion/deletion, alpha adducin (ADD1) G460W, and IL-10 gene polymorphisms, and determination of prognostic effects in idiopathic sudden sensorineural hearing loss

ObjectiveThe aim of this study was to examine angiotensin converting enzyme (ACE) insertion/deletion, alpha adducin, and interleukin-10 (IL-10) gene polymorphisms (GPs) in terms of both idiopathic sudden sensorineural hearing loss (ISSNHL) risk and their potential prognostic effects. MethodsThe study group consisted of 70 patients and the control group consisted of 50 patients. Venous blood samples were analyzed for relevant GPs via kompetitive allele-specific polymerase chain reaction. Age, sex, affected side, tinnitus, and vertiginous symptom status, number of days between symptom onset and hospital admission, pure tone audiometry results at admission and after treatment were included in the study. Data were compared statistically. ResultsThe D allele of ACE insertion/deletion GP was significantly more frequent in patients with ISSNHL than in the control group (p = 0.032). II genotype was associated with a reduced risk of ISSNHL (p = 0.036). The amount of hearing loss was significantly higher in patients with the TT genotype (p = 0.027) and T allele of the IL-10 GP (p = 0.035) than in the patients without this allele. Severe hearing loss was a poor prognostic factor (p = 0.008). ConclusionsThe D allele of ACE insertion/deletion GP may be involved in the ISSNHL etiology. Due to the association of this allele with occlusive vascular pathologies, ischemia is believed to be a common pathway in the etiopathogenesis of ISSNHL.

Interleukin-17 Genotypes in Egyptian Asthmatic Children at Zagazig University Hospitals.

Bronchial asthma (BA) is increasing among Egyptian children. It is affected by multiple factors including genetic ones. In the current study, we assessedthe relationship between interleukin-17 (IL-17) genotypes and the occurrence of BA among Egyptian children. This case-control study included 100 participants. Group I (the control group) comprised 50 healthy subjects. Group II (the asthmatic group) comprised 50 subjects diagnosed with atopic asthma according tothe Global Initiative for Asthma. Measurement of serum Ig E and eosinophilic count was performed. Detection of single nucleotide polymorphism rs2275913 of IL-17 gene by restriction fragment length polymorphism-polymerase chain reaction was conducted. GA and AA genotypes were more frequent in the asthmatic group compared tothe control group (P = 0.03 and 0.01, respectively). Subjects carrying GA and AA genotypes were more susceptibleto have asthma [odds ratio (OR) = 2.21, 95% confidence interval (CI) = 1.14-9.94, P = 0.03; OR = 7.78, 95% CI = 1.59-38.3, P = 0.01, respectively]. The A allele was higher in the asthmatic group (33%) compared tothe control group (10%). A allele carriers were more susceptibleto have asthma (OR = 4.43, 95% CI = 2.04-9.82 and P < 0.001). Immunoglobulin E (IgE) levels and eosinophil percentages were higher among the carriers of GA and AA genotypes when compared with the GG genotype. All pulmonary function tests were significantly lower among carriers of AA genotype compared with GG genotype. An A allele carrier, AA genotype, increased IgE level, and eosinophil level were significant predictors for occurrence of asthma (P = 0.01, 0.02, 0.004, and 0.01). In conclusion, AA genotype carriers and A allele carriers of the IL-17 gene are more likely to have asthma compared with controls.

Association of the Single Nucleotide Polymorphisms rs11556218, rs4778889, rs4072111, and rs1131445 of the Interleukin-16 Gene with Ovarian Cancer.

Single nucleotide polymorphisms (SNPs) of the IL-16 gene have been reported to influence the risk of several cancers, but their role in ovarian cancer (OC) has not been studied. Using the restriction fragment length polymorphism (PCR-RFLP) method, we examined four IL-16 SNPs: rs11556218 (T > G), rs4778889 (T > C), rs4072111 (C > T), and rs1131445 (T > C) in blood samples from 413 women of Central European descent, including 200 OC patients and 213 healthy controls. Among the patients, 62% were postmenopausal, 84.5% were diagnosed in late stages (FIGO IIb-IV), and 73.5% had high-grade serous OC (HGSOC). Minor allele frequencies in controls were 9.2% for rs11556218 (G allele), 13.7% for rs4778889 (C allele), 10.4% for rs4072111 (T allele), and 32.3% for rs1131445 (C allele). We found significant associations of rs11556218 (G vs. T allele: OR 2.76, 95% CI 1.84-4.14, p < 0.0001) with elevated OC risk in the whole cohort (p < 0.001) and in both premenopausal (p < 0.001) and postmenopausal (p = 0.001) subgroups. These associations remained significant across heterozygote (p < 0.001), dominant (p < 0.001), and overdominant (p < 0.001) models. IL-16 rs4778889 was associated with OC risk predominantly in premenopausal women (p < 0.0001 in almost all models). In the whole cohort, the C allele was associated with OC risk (OR 1.54, CI 95% 1.06-2.23, p = 0.024), and the association of rs4778889 was significant in dominant (p = 0.019), overdominant (p = 0.033), and heterozygote (p = 0.027) models. Furthermore, rs4778889 was linked with HGSOC (p = 0.036) and endometriosis-related OC subtypes (p = 0.002). No significant associations were found for rs4072111 or rs1131445 (p = 0.81 or 0.47, respectively). In conclusion, rs11556218 and rs4778889 SNPs are associated with OC risk, especially in premenopausal women.

Interleukin-10: Genetic association and biochemical prediction of sepsis-induced AKI in ICU critically ill patients: A cross-sectional study.

Sepsis is a potentially life-threatening condition that eventually causes multi-organ dysfunction in critically ill patients. Acute kidney injury (AKI) is a widespread and severe threatening complication of sepsis, a condition termed sepsis-induced AKI (S-AKI), with poor clinical outcomes and high mortality rates. Inflammatory and immunological responses are important variables in S-AKI. This study aimed to examine the relationship of rs1518111 polymorphism in the interleukin-10 (IL-10) gene and serum/urine IL-10 levels with sepsis-induced AKI in critically ill patients in the ICU. In this cross-sectional study, 310 critically ill adult patients were recruited, of whom, 197 developed S-AKI. Real-time PCR was performed to detect the rs1518111 polymorphism. Circulating blood and urine IL-10 levels of IL-10 were measured. For rs1518111 SNP, the presence of at least one T allele increased the risk of occurrence of S-AKI in critically ill patients with sepsis (OR: 1.34, 95% CI: 1.07-3.17; p ˂ 0.001), regardless of the type of infection and severity of sepsis. Blood and urine IL-10 levels were an excellent prediction of S-AKI (AUC: 0.881 and 0.953 and sensitivity: 90.2% and 97.6% at cutoff 133.5 and 5.67 pg/mL, respectively). Regression analysis showed that WBC count and increased blood and urine IL-10 levels, in addition to the presence of TT genotype, are independent risk factors for AKI. rs1518111 polymorphism in the IL-10 gene is a risk factor for sepsis-induced AKI in the ICU. Serum/urine IL-10 markers may be used as early predictors of S-AKI in critically ill patients with sepsis, thereby improving early management.

Pharmacogenetic analysis of interleukin-10 variants and tacrolimus metabolism in kidney transplant patients from Pakistani population.

End stage renal disease (ESRD) occurs when the kidneys are unable to filter the waste products and excessive fluids from the blood that results into the accumulation of toxins and fluid in the body. Tacrolimus is commonly used immunosuppressant while sirolimus and cyclosporin are rarely used drugs to stop solid organ transplant rejection. The host's immunological response following transplantation produces interleukin-10 (IL-10), which influences the varied CYP3A-dependent drug disposition of tacrolimus. The aim of this study was to determine the genetic polymorphisms of IL-10 (rs1800871, rs1800872 and rs1800896) gene associated with tacrolimus metabolism in kidney transplant patients from Lahore Punjab, Pakistan. The study collected blood samples of 103 healthy individuals and 137 kidney transplant patients as control and treatment groups, respectively. We employed Tetra ARMS PCR for the genotype analysis of extracted DNA. The alleles were called on 2% agarose gel. Moreover, the study utilized SPSS software to analyze statistical significance of polymorphism. It was found that genotypic frequencies of IL-10 (rs1800871), IL-10 (rs1800872), and IL-10 (rs1800896) were (TT: 66.4%; TC: 31.4%; CC: 2.2%), (AA: 27.7%; AC: 54%; CC: 18.2%), (AA: 64.2%; GA: 17.5%; GG: 18.3%), respectively among kidney transplant patients. All parameters show significant association at different points after transplantation. Genetic analysis showed that TC and CC genotypes in rs1800871 (OR (95%CI) = 5.721 (3.231-10.131), P < 0.001; OR (95%CI) = 3.370 (0.642-17.672), P = 0.150), AC and CC genotypes in rs1800872 (OR (95%CI) = 1.294 (0.695-2.410), P = 0.415; OR (95%CI) = 1.453 (0.671-3.147), P = 0.342), GA and GG genotypes in rs1800896 (OR (95%CI) = 42.952 (17.566-105.021), P = 0.001; OR (95%CI) = 7.040 (2.563-19.333), P = 0.342) was associated with risk of renal rejection in kidney transplant patients. Besides, genetic models showed that TT in rs1800871, AA genotypes in rs1800872 and rs1800892 were associated with risk of renal rejection under dominant model when compared to controls (OR (95%CI) = 5.721 (3.231-10.131), P < 0.001; OR (95%CI) = 1.335 (0.735-9.290), P < 0.341; OR (95%CI) = 24.629 (10.599-57.230), P < 0.001), respectively. From the results, it is concluded that genetic polymorphism of IL-10 (rs1800871, rs1800872 and rs1800896) has a highly significant association with risk of renal rejection in Pakistani kidney transplant patients.

The Enigmatic Interplay of Interleukin-10 in the Synergy of HIV Infection Comorbid with Preeclampsia.

Cytokines coordinate the intricate choreography of the immune system, directing cellular activities that mediate inflammation, pathogen defense, pathology and tissue repair. Within this spectrum, the anti-inflammatory prowess of interleukin-10 (IL-10) predominates in immune homeostasis. In normal pregnancy, the dynamic shift of IL-10 across trimesters maintains maternal immune tolerance ensuring fetal development and pregnancy success. Unravelling the dysregulation of IL-10 in pregnancy complications is vital, particularly in the heightened inflammatory condition of preeclampsia. Of note, a reduction in IL-10 levels contributes to endothelial dysfunction. In human immunodeficiency virus (HIV) infection, a complex interplay of IL-10 occurs, displaying a paradoxical paradigm of being immune-protective yet aiding viral persistence. Genetic variations in the IL-10 gene further modulate susceptibility to HIV infection and preeclampsia, albeit with nuanced effects across populations. This review outlines the conceptual framework underlying the role of IL-10 in the duality of normal pregnancy and preeclampsia together with HIV infection, thus highlighting its regulatory mechanisms and genetic influences. Synthesizing these findings in immune modulation presents avenues for therapeutic interventions in pregnancy complications comorbid with HIV infection.

Microglia-specific IL-10 gene delivery inhibits neuroinflammation and neurodegeneration in a mouse model of Parkinson's disease.

Neuroinflammation plays a key role in exacerbating dopaminergic neuron (DAN) loss in Parkinson's disease (PD). However, it remains unresolved how to effectively normalize this immune response given the complex interplay between the innate and adaptive immune responses occurring within a scarcely accessible organ like the brain. In this study, we uncovered a consistent correlation between neuroinflammation, brain parenchymal lymphocytes, and DAN loss among several commonly used mouse models of PD generated by a variety of pathological triggers. We validated a viral therapeutic approach for the microglia-specific expression of interleukin 10 (IL-10) to selectively mitigate the excessive inflammatory response. We found that this approach induced a local nigral IL-10 release that alleviated DAN loss in mice overexpressing the human SNCA gene in the substantia nigra. Single-cell transcriptomics revealed that IL-10 induced the emergence of a molecularly distinct microglial cell state, enriched in markers of cell activation with enhanced expression of prophagocytic pathways. IL-10 promoted microglial phagocytotic and clearance activities in vitro and reduced αSYN aggregate burden in the nigral area in mice overexpressing SNCA. Furthermore, IL-10 stimulated the differentiation of CD4+ T lymphocytes into active T regulatory cells and promoted inhibitory characteristics in CD8+ T cells. In summary, our results show that local and microglia-specific IL-10 transduction elicited strong immunomodulation in the nigral tissue with enhanced suppression of lymphocyte toxicity that was associated with DAN survival. These results offer insights into the therapeutic benefits of IL-10 and showcase a promising gene delivery approach that could minimize undesired side effects.

Impacts of Interleukin-10 Promoter Genotypes on Prostate Cancer.

Prostate cancer (PCa) is a multifactorial disease influenced by genetic, environmental, and immunological factors. Genetic polymorphisms in the interleukin-10 (IL-10) gene have been implicated in PCa susceptibility, development, and progression. This study aims to assess the contributions of three IL-10 promoter single nucleotide polymorphisms (SNPs), A-1082G (rs1800896), T-819C (rs3021097), and A-592C (rs1800872), to the risk of PCa in Taiwan. The three IL-10 genotypes were determined using PCR-RFLP methodology and were evaluated for their contributions to PCa risk among 218 PCa patients and 436 non-PCa controls. None of the three IL-10 SNPs were significantly associated with the risks of PCa (p all > 0.05) in the overall analyses. However, the GG at rs1800896 combined with smoking behavior was found to significantly increase the risk of PCa by 3.90-fold (95% confidence interval [95% CI] = 1.28-11.89, p = 0.0231). In addition, the rs1800896 AG and GGs were found to be correlated with the late stages of PCa (odds ratio [OR] = 1.90 and 6.42, 95% CI = 1.05-3.45 and 2.30-17.89, p = 0.0452 and 0.0003, respectively). The IL-10 promoter SNP, A-1082G (rs1800896), might be a risk factor for PCa development among smokers and those at late stages of the disease. These findings should be validated in larger and more diverse populations.

Mass vaccination with reassortment-impaired live H9N2 avian influenza vaccine

Avian influenza poses a severe threat to poultry production and global food security, prompting the development of vaccination programs in numerous countries. Modified live virus (MLV) vaccines, with their potential for mass application, offer a distinct advantage over existing options. However, concerns surrounding reversion, recombination, and unintended transmission have hindered the progress of MLV development for avian influenza in poultry. To address these concerns, we engineered reassortment-impaired, non-transmissible, safe, immunogenic, and protective MLVs through the rearrangement of internal gene segments and additional modifications to the surface gene segments HA and NA. The unique peptide marker aspartic acid-arginine-proline-alanine-valine-isoleucine-alanine-asparragine (DRPAVIAN) was incorporated into HA, while NA was modified to encode the chicken interleukin-18 (ckIL18) gene (MLV-H9N2-IL). In vitro, the MLV-H9N2 and MLV-H9N2-IL candidates demonstrated stability and virus titers comparable to the wild-type H9N2 strain. In chickens, the MLV-H9N2 and MLV-H9N2-IL candidates did not transmit via direct contact. Co-infection studies with wild-type virus confirmed that the altered HA and NA segments exhibited fitness disadvantages and did not reassort. Vaccinated chickens showed no clinical signs upon vaccination, all seroconverted, and the inclusion of ckIL18 in the MLV-H9N2-IL vaccine enhanced neutralizing antibody production. A significant decrease in viral loads post-challenge underscored the protective effect of the MLVs. The MLV-H9N2-IL vaccine, administered via drinking water, proved immunogenic in chickens in a dose-dependent manner, generating protective levels of neutralizing antibodies upon aggressive homologous virus challenge. In summary, this study lays the groundwork for safe MLVs against avian influenza suitable for mass vaccination efforts.

Evolutionary Analysis of the Mammalian IL-17 Cytokine Family Suggests Conserved Roles in Female Fertility.

The interleukin-17 (IL-17) family includes pro-inflammatory cytokines IL-17A-F with important roles in mucosal defence, barrier integrity and tissue regeneration. IL-17A can be dysregulated in fertility complications, including pre-eclampsia, endometriosis and miscarriage. Because mammalian subclasses (eutherian, metatherian, and prototherian) have different related reproductive strategies, IL-17 genes and proteins were investigated in the three mammalian classes to explore their involvement in female fertility. Gene and protein sequences for IL-17s are found in eutherian, metatherian and prototherian mammals. Through synteny and multiple sequence protein alignment, the relationships among mammalian IL-17s were inferred. Publicly available datasets of early pregnancy stages and female fertility in therian mammals were collected and analysed to retrieve information on IL-17 expression. Synteny mapping and phylogenetic analyses allowed the classification of mammalian IL-17 family orthologs of human IL-17. Despite differences in their primary amino acid sequence, metatherian and prototherian IL-17s share the same tertiary structure as human IL-17s, suggesting similar functions. The analysis of available datasets for female fertility in therian mammals shows up-regulation of IL-17A and IL-17D during placentation. IL-17B and IL-17D are also found to be over-expressed in human fertility complication datasets, such as endometriosis or recurrent implantation failure. The conservation of the IL-17 gene and protein across mammals suggests similar functions in all the analysed species. Despite significant differences, the upregulation of IL-17 expression is associated with the establishment of pregnancy in eutherian and metatherian mammals. The dysregulation of IL-17s in human reproductive disorders suggests them as a potential therapeutic target.

The evaluation of IL-4 VNTR intron 3 and TNF-α (rs1799964) gene polymorphisms in Egyptian patients with alopecia areata: a case–control study

BackgroundAlopecia areata (AA) is a non-scarring hair loss condition that usually affects the scalp. The exact pathogenesis is poorly understood; however, multiple factors like genetics, environmental, psychological, and immunological factors may have a role. The purpose of this study was to look into possible links between the functional interleukin-4 (IL-4) gene intron 3 variable number of tandem repeats (VNTR) and TNF-(rs1799964) gene polymorphism and AA susceptibility. This case–control study consisted of 79 unrelated patients and 156 age- and sex-matched healthy individuals as a control group. The Severity of Alopecia Tool was used to assess the extent of hair loss from the scalp. Polymerase chain reaction (PCR) with specific primers was used to determine IL-4 gene 70-bp VNTR polymorphism while polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) was used to investigate TNF-α (rs1799964) gene polymorphism.ResultsNone of the selected polymorphisms for both genotypes and alleles had statistical significance when patients and controls were compared with each other (p-values for IL-4 VNTR were 0.11, 0.74, 0.052 and 0.27 and for TNF-α polymorphism was 0.71, 0.43, 0.65 and 0.55, respectively, for codominant, dominant, recessive and overdominant models of inheritance, respectively). Furthermore, the same results were retrieved when the genotypes were compared with the patient’s clinical and demographic data (p-value > 0.05).ConclusionThe findings indicate that IL-4 VNTR intron 3 and TNF-α (rs1799964) gene polymorphisms are not linked to the development of AA in the Egyptian population.

Dietary Triple-Strain Bacillus-Based Probiotic Supplementation Improves Performance, Immune Function, Intestinal Morphology, and Microbial Community in Weaned Pigs.

Probiotics provide health benefits and are used as feed supplements as an alternative prophylactic strategy to antibiotics. However, the effects of Bacillus-based probiotics containing more than two strains when supplemented to pigs are rarely elucidated. SOLVENS (SLV) is a triple-strain Bacillus-based probiotic. In this study, we investigate the effects of SLV on performance, immunity, intestinal morphology, and microbial community in piglets. A total of 480 weaned pigs [initial body weight (BW) of 8.13 ± 0.08 kg and 28 days of age] were assigned to three treatments in a randomized complete block design: P0: basal diet (CON); P200: CON + 200 mg SLV per kg feed (6.5 × 108 CFU/kg feed); and P400: CON + 400 mg SLV per kg feed (1.3 × 109 CFU/kg feed). Each treatment had 20 replicated pens with eight pigs (four male/four female) per pen. During the 31 d feeding period (Phase 1 = wean to d 14, Phase 2 = d 15 to 31 after weaning), all pigs were housed in a temperature-controlled nursery room (23 to 25 °C). Feed and water were available ad libitum. The results showed that the pigs in the P400 group increased (p < 0.05) average daily gain (ADG) in phase 2 and tended (p = 0.10) to increase ADG overall. The pigs in the P200 and P400 groups tended (p = 0.10) to show improved feed conversion ratios overall in comparison with control pigs. The pigs in the P200 and P400 groups increased (p < 0.05) serum immunoglobulin A, immunoglobulin G, and haptoglobin on d 14, and serum C-reactive protein on d 31. The pigs in the P200 group showed an increased (p < 0.01) villus height at the jejunum, decreased (p < 0.05) crypt depth at the ileum compared with other treatments, and tended (p = 0.09) to have an increased villus-crypt ratio at the jejunum compared with control pigs. The pigs in the P200 and P400 groups showed increased (p < 0.05) goblet cells in the small intestine. Moreover, the pigs in the P400 group showed down-regulated (p < 0.05) interleukin-4 and tumor necrosis factor-α gene expressions, whereas the pigs in the P400 group showed up-regulated occludin gene expression in the ileum. These findings suggest that SLV alleviates immunological reactions, improves intestinal microbiota balance, and reduces weaning stress in piglets. Therefore, SOLVENS has the potential to improve health and performance for piglets.

Study of the relationship between genetic variants of IL-18 and the occurrence of inflammatory bowel disease

BackgroundA member of the Interleukin-1 superfamily of cytokines, interleukin-18 (IL-18) is essential to the etiology and progression of inflammatory bowel disease (IBD), a chronic inflammatory illness that affects the digestive system. This study investigated the possible association between two genetic variations, IL-18 rs187238 and IL-18 rs1946518, and IBD in Iraqi patients.MethodsWe evaluated the association of two SNPs of the IL-18 gene at rs187238 and rs1946518 in 54 IBD patients with 19 Crohn’s disease (CD), 35 ulcerative colitis (UC), and 46 healthy controls using PCR-RFLP and PCR-AS techniques for detecting IL-18 rs187238 and IL-18 rs1946518, respectively, by extracting genomic DNA from blood samples.ResultsOur findings indicated no statistically significant variations between the IL-18 rs187238 genotypes and incidences of CD and UC (P = 0.189 and 0.59, respectively). However, the allele frequency showed a significant difference with CD (P = 0.049) but did not show a significant association with UC (P = 0.887). There was no significant association between the genotype and allele frequency of IL-18 rs1946518C/A and CD risk (P = 0.171 and 0.053, respectively). However, there was a significant association between the genotype and allele frequency of IL-18 rs1946518C/A and the risk of developing UC (P = 0.028 and 0.002, respectively).ConclusionThe study revealed statistically significant distinctions between the genetic and allelic frequencies of IL-18 rs1946518 and the probability of developing UC. Nonetheless, there were no significant distinctions between them and CD. According to the research, there were no major differences between IL-18 rs187238 and the two diseases. The frequency of the C allele is connected to CD.

The Assessment of Interleukin-15 and Interleukin-21 Gene Expression and Serum Level in Celiac Disease Prevalence Patients

Eighty-four Iraqi patients (Male &amp; Female) with celiac disease with an age range (3-65) were investigated. Samples were taken from the Al Karama Teaching Hospital period October 2020 - to June 2021. Data sheet was filled according to questionnaire format, which include name, age, smoking, family history &amp; alcohol intake. The patient's diagnosis was based on some serological test (AGA, tTG) the patients were clinically subdivided into treated and untreated. Twenty- seven controls were selected randomly from apparently healthy individual (31 male &amp; 53 female). This study aims to evaluate evaluated some genetic &amp; immunological parameters; her were: 1-Determine whether the gene expression and the serum level of interleukins (15 and 21) have an effect on the functioning of the immune system in individuals with celiac disease. 2-Evaluated CD gene expression of treated (gluten-free diet) and naive (untreated) CD patients compared with healthy individuals. The study methodology was based on an ELISA test kit provides a quantitative in vitro assay for human autoantibodies of the IgA class against tissue transglutaminase in serum or plasma. Result shown in Table (2) indicate that the majority of patients in celiac disease were diagnosed in females more than males; in the other hand, 66,67% of the confirmed treated Patients with celiac disease were females, while 33.33% were males, 40% confirmed untreated Patients from celiac disease were males when they were females 60 %, moreover furthermore 62.96% control female group more than 37.04% male control group with a significant difference (P-value 0.03661). The collected data showed that 23 (76.67%) patients had no clinical history of celiac disease in the untreated group; on the other hand, only 7 (23.33%) had a clinical history of the patient in the same group, while 1 (3.7%) ) The group of patients treated with no clinical history more than 26 (96.30%) and the patient in the same group had a clinical history, as well as 20 (74.07%) patients, had no history of celiac disease in the control group 7 (25.93%) Patients with a family history of celiac disease in the control group, with highly significant difference * (P≤0.05), ** (P≤0.01), (P-value 0.0001). he casuistic in table (3) showed the serum of 84 patients, including 30 with celiac disease without treatment tTG-IgA (5.41 ±0.27 b), tTG-IgG (3.76 ±0.27 b),27 patients treated group tTG-IgA (10.65 ±1.84 a), tTG-IgG (7.31 ±1.46 a) and 27 healthy as controls tTG-IgA (3.62 ±0.19 b), tTG-IgG (2.72 ±0.17 b), with P-value tTG-IgA (0.0001), tTG-IgG (0.0007), within significantly high difference ** (P≤0.01). The variants represented IL-15 and IL-21 gene expressions of celiac patients untreated, treated group, compared with that in the healthy control group individuals. The results showed that of IL-21 expression in untreated patients was (27.22 ±0.23 a) tables (6) and (7), while treated group (27.37 ±0.24 a), more than control group (25.04 ±0.53 b), with high significant P-Value (P≤0.01). At the same time, the expression of the IL-15 gene in untreated patient was (29.50 ±0.40), while treated group (29.63 ±0.26a) and control group (29.04 ±0.81), with non-significant P-Value (P≤0.706).

Assessment of Interleukin 10 (IL-10) Single Nucleotide Polymorphism (SNP) in Irritable Bowel Syndrome (IBS) Patients

Abstract Background Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder characterized by the presence of abdominal pain, bloating and altered bowel habits. The pathophysiological mechanisms underlying IBS are unclear. The abnormalities of motility, visceral hypersensitivity, gut microbial alteration and psychological stress contribute to the clinical symptoms of IBS. The associations of IBS and its risk gene polymorphisms have been ascertained by many researchers. Single nucleotide polymorphisms (SNPs) represent the most widespread type of sequence variations in genomes. It is known to be valuable genetic markers, because it may reveal the evolutionary history and common genetic polymorphisms that explain the hereditary risks for common diseases. Cytokines are involved in the pathogenesis of IBS. To date, only a few studies concerned the association of interleukin-10 (IL-10) gene polymorphism (rs1800871) -819 position to IBS. Objective We assessed interleukin 10 (IL-10) single nucleotide polymorphism rs1800871 (-819 C/T) in IBS patients. Method This was comparative case - control study for 40 participants, 20 cases and 20 controls, IL-10 rs1800871 (−819 T/C) single nucleotide polymorphism (SNP) was done via real time polymerase chain reaction for both study groups to assess its relation with IBS. Results The studied participants were divided into two groups according to ROME IV _criteria. For the case group (n = 20), the mean age was 41.05 ± 17.45 years, with 50% being male and 50% being female. In the control group (n = 20), mean age was 39.80 ± 14.84 years, with 25% being male and 75% being female Compared to the controls subjects, the frequencies of the IL-10 -819 T/T genotype and T allele were observed to be overrepresented in patients with IBS (60%; odds ratio [OR] = 1.143; 95% confidence interval [CI]: (0.152 – 8.593) for the TT genotype; P = 0.897) and (72.5%; OR: 1.582; 95% CI: (0.615 – 4.066)for the T allele; P = 0.341, respectively). The results demonstrated that T/T genotype was the most common genotype in the case group (60%). T allele was the most prevalent in case group (72.5%), while the C allele was the least prevalent (27.5%). However, T/T polymorphism in cases was greater than in control with non- statistical significance (p = 0.157). Conclusion IL-10 polymorphism (rs-1800871) has no association with IBS, However, T/T genotype was shown frequently in cases, with strong association with IBS. Abbreviations: IBS (irritable bowel syndrome), IL-10 (Interleukin-10 cytokine), SNP (single nucleotide polymorphism)

Relationship between the serum level, polymorphism and gene expression of IL-33 in samples of recurrent miscarriage Iraqi women infected with toxoplasmosis

One of the many warm-blooded hosts that toxoplasmosis-causing intracellular protozoan parasite Toxoplasma gondii can infect is humans. Cytokines are crucial to stimulate an effective immune response against T. gondii. Interleukin-33 (IL-33) is a unique anti-inflammatory cytokine that suppresses the immune response. The levels of cytokine gene expression are regulated by genetics, and the genetic polymorphisms of these cytokines play a functional role in this process. Single nucleotide polymorphisms (SNPs) are prognostic indicators of illnesses. This study aimed to determine whether toxoplasmosis interacts with serum levels of IL-33 and its SNP in miscarriage women as well as whether serum levels and IL-33 gene expression are related in toxoplasmosis-positive miscarriage women. Two hundred blood samples from patients and controls were collected from AL-Alawiya Maternity Teaching Hospital and AL-Yarmouk Teaching Hospital in Baghdad, Iraq from 2021 to 2022 in order to evaluate the serum level of IL-33 using ELISA test. For the SNP of IL-33, the allelic high-resolution approach was utilized, and real time-PCR was performed to assess gene expression. The results showed that compared to healthy and pregnant women, recurrent miscarriage with toxoplasmosis and recurrent miscarriage women had lower IL-33 concentrations. Additionally, there were significant differences among healthy women, pregnant women, and women with repeated miscarriage who experienced toxoplasmosis. Furthermore, no differences between patients and controls were revealed by gene expression data. The results revealed that recurrent miscarriage, pregnancy, and healthy women all had a slightly higher amount of the IL-33 gene fold. Additionally, the SNP of IL-33 data demonstrated that there was no significant genetic relationship between patients and controls. Recurrent miscarriage women with toxoplasmosis have showed significant differences from pregnant women in the genotypes GG and AA as well as the alleles A and G. There were notable variations between recurrent miscarriage with and without toxoplasmosis in terms of the genotypes AA and AC. The genotypes GG, AA, and allele A in recurrent miscarriage women with toxoplasmosis and recurrent miscarriage women is a protective factor. Taking together, there was a statistically significant negative correlation between toxoplasmosis and IL-33 gene expression, which calls for more quantitative investigation in order to fully comprehend the interaction of mRNA and protein.