Expression Of Interleukin Research Articles

Interleukin-12 Delivery Strategies and Advances in Tumor Immunotherapy.

Interleukin-12 (IL-12) is considered to be a promising cytokine for enhancing an antitumor immune response; however, recombinant IL-12 has shown significant toxicity and limited efficacy in early clinical trials. Recently, many strategies for delivering IL-12 to tumor tissues have been developed, such as modifying IL-12, utilizing viral vectors, non-viral vectors, and cellular vectors. Previous studies have found that the fusion of IL-12 with extracellular matrix proteins, collagen, and immune factors is a way to enhance its therapeutic potential. In addition, studies have demonstrated that viral vectors are a good platform, and a variety of viruses such as oncolytic viruses, adenoviruses, and poxviruses have been used to deliver IL-12-with testing previously conducted in various cancer models. The local expression of IL-12 in tumors based on viral delivery avoids systemic toxicity while inducing effective antitumor immunity and acting synergistically with other therapies without compromising safety. In addition, lipid nanoparticles are currently considered to be the most mature drug delivery system. Moreover, cells are also considered to be drug carriers because they can effectively deliver therapeutic substances to tumors. In this article, we will systematically discuss the anti-tumor effects of IL-12 on its own or in combination with other therapies based on different delivery strategies.

Prognostic Impact of Acute and Chronic Inflammatory Interleukin Signatures in the Tumor Microenvironment of Early Breast Cancer

Interleukins play dual roles in breast cancer, acting as both promoters and inhibitors of tumorigenesis within the tumor microenvironment, shaped by their inflammatory functions. This study analyzed the subtype-specific prognostic significance of an acute inflammatory versus a chronic inflammatory interleukin signature using microarray-based gene expression analysis. Correlations between these interleukin signatures and immune cell markers (CD8, IgKC, and CD20) and immune checkpoints (PD-1) were also evaluated. This study investigated the prognostic significance of an acute inflammatory IL signature (IL-12, IL-21, and IFN-γ) and a chronic inflammatory IL signature (IL-4, IL-5, IL-10, IL-13, IL-17, and CXCL1) for metastasis-free survival (MFS) using Kaplan–Meier curves and Cox regression analyses in a cohort of 461 patients with early breast cancer. Correlations were analyzed using the Spearman–Rho correlation coefficient. Kaplan–Meier curves revealed that the prognostic significance of the acute inflammatory IL signature was specifically pronounced in the basal-like subtype (p = 0.004, Log Rank). This signature retained independent prognostic significance in multivariate Cox regression analysis (HR 0.463, 95% CI 0.290–0.741; p = 0.001). A higher expression of the acute inflammatory IL signature was associated with longer MFS. The chronic inflammatory IL signature showed a significant prognostic effect in the whole cohort, with higher expression associated with shorter MFS (p = 0.034). Strong correlations were found between the acute inflammatory IL signature and CD8 expression (ρ = 0.391; p < 0.001) and between the chronic inflammatory IL signature and PD-1 expression (ρ = 0.627; p < 0.001). This study highlights the complex interaction between acute and chronic inflammatory interleukins in breast cancer progression and prognosis. These findings provide insight into the prognostic relevance of interleukin expression patterns in breast cancer and may inform future therapeutic strategies targeting the immune–inflammatory axis.

The Prospect of Improving Pancreatic Cancer Diagnostic Capabilities by Implementing Blood Biomarkers: A Study of Evaluating Properties of a Single IL-8 and in Conjunction with CA19-9, CEA, and CEACAM6.

Background/Objectives: This study aims to evaluate the possible clinical application of interleukin 8 (IL-8) as a single biomarker and its capabilities in combination with carbohydrate antigen (CA19-9), carcinoembryonic antigen (CEA), and carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6) as diagnostic and prognostic tools for pancreatic ductal adenocarcinoma (PDAC). Methods: A total of 170 serum samples from patients with PDAC (n = 100), chronic pancreatitis (CP) (n = 39), and healthy individuals (n = 31) were analysed. IL-8 and CEACAM6 were measured by an enzyme-linked immunosorbent assay (ELISA). CA19-9 and CEA were determined by chemiluminescent microparticle immunoassay, and bilirubin was quantified using a diazonium salt reaction. Receiver operating characteristic curve analysis, logistic regression, and Kaplan-Meier analyses were performed to evaluate the properties of a single IL-8 and in combination with other biomarkers. Results: The concentrations of IL-8 were statistically significantly higher in the PDAC group compared to the CP and control groups. Heterogeneous levels of IL-8 correlated with PDAC stages (p = 0.007). IL-8 had good and satisfactory diagnostic efficacy in differentiating PDAC from controls (0.858; p < 0.001) and patients with CP (0.696; p < 0.001), respectively. High and low expressions of IL-8 were not significantly associated with overall survival (OS) or disease-free survival (DFS). A combination of IL-8, CEACAM6, and CA19-9 reached the highest AUC values for differentiating PDAC from the control group. The best classification score between PDAC and the control group with CP patients was obtained by merging IL-8 and CA19-9 (0.894; p < 0.001). Conclusions: These results provide compelling evidence of IL-8 as a promising diagnostic biomarker. Nonetheless, due to the high complexity of PDAC, only the conjunction of IL-8, CA19-9, and CEACAM6 integrates sufficient diagnostic capabilities.

Interleukin-35: A key player managing pre-diabetes and chronic inflammatory type 1 autoimmune diabetes.

Interleukin-35 (IL-35) is a novel protein comprising IL-12α and IL-27β chains. The IL12A and EBI3 genes are responsible for its production. The study of IL-35 has experienced a substantial increase in interest in recent years, as demonstrated by many research papers. Recent clinical studies have shown that individuals who do not have a C-peptide have notably reduced amounts of IL-35 in their blood serum. This is accompanied by a drop in the percentage of IL-35+ Treg cells, regulatory B cells, and CD8+ FOXP3+ cells that produce IL-35. This article em-phasizes the potential significance of IL-35 expression in governing the immune response and its involvement in chronic inflammatory autoimmune diabetes in pancreatic inflammation. It demonstrates IL-35's ability to regulate cytokine proportions, modulate B cells, and protect against autoimmune diabetes. However, further investigation is necessary to ascertain the precise mechanism of IL-35, and meticulous planning is essential for clinical studies.

Bromodomain-Containing 4 Is a Positive Regulator of Interleukin-34 Production in the Gut.

Experimental evidence suggests that, in the inflamed gut of inflammatory bowel disease (IBD) patients, interleukin-34 (IL-34) triggers detrimental signaling pathways. Factors/mechanisms regulating IL-34 production in IBD remain poorly characterized. Bromodomain-containing 4 (BRD4), a transcriptional and epigenetic regulator, is over-expressed in IBD, and studies in cancer cells suggest that BRD4 might positively control IL-34 expression. This study aimed to assess whether, in IBD, BRD4 regulates IL-34 expression. In IBD, there was an up-regulation of both IL-34 and BRD4 compared to the controls, and the two proteins co-localized in both lamina propria mononuclear cells (LPMCs) and epithelial cells. Flow cytometry analysis of CD45+ LPMCs confirmed that the percentages of IL-34- and BRD4-co-expressing cells were significantly higher in IBD than in the controls and showed that more than 80% of the IL-34-positive CD45-LPMCs expressed BRD4. IL-34 and BRD4 were mainly expressed by T cells and macrophages. IL-34 expression was reduced in IBD LPMCs transfected with BRD4 antisense oligonucleotide and in the colons of mice with dextran sulfate sodium-induced colitis treated with JQ1, a pharmacological inhibitor of BRD4. These data indicate that BRD4 is a positive regulator of IL-34 in IBD, further supporting the pathogenic role of BRD4 in IBD-associated mucosal inflammation.

Didymin Ameliorates Dextran Sulfate Sodium (DSS)-Induced Ulcerative Colitis by Regulating Gut Microbiota and Amino Acid Metabolism in Mice.

Background: Didymin is a dietary flavonoid derived from citrus fruits and has been shown to have extensive biological functions, especially anti-inflammatory effects, but its mechanism is unclear. The purpose of this study was to investigate the potential mechanism of didymin that alleviates ulcerative colitis. Methods and Results: Our results indicated that didymin could alleviate the symptoms of ulcerative colitis, as it inhibited the expressions of interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Didymin also promoted the expressions of claudin-1 and zona occludens-1(ZO-1), which are closely related with restoring colon barrier function. Didymin also increased the abundance of Firmicutes and Verrucomicobiota, while decreasing the abundance of Bacteroidota and Proteobacteria. Meanwhile, didymin significantly altered the levels of metabolites related to arginine synthesis and metabolism, and lysine degradation in the colitis mice. Utilizing network pharmacology and molecular docking, our results showed that the metabolites L-ornithine and saccharin could interact with signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa-B (NF-κB). In this in vitro study, L-ornithine could reduce the expressions of transcription factors STAT3 and NF-κB, and it also inhibited the expressions of IL-6 and IL-1β in the lipopolysaccharides (LPS) induced in RAW264.7 cells, while saccharin had the opposite effect. Conclusions: Taken together, didymin can regulate gut microbiota and alter metabolite products, which can modulate STAT3 and NF-κB pathways and inhibit the expressions of inflammatory factors and inflammatory response in the DSS-induced colitis mice.

Low-intensity pulsed ultrasound regulates bone marrow mesenchymal stromal cells differentiation and inhibits bone loss by activating the IL-11-Wnt/β-catenin signaling pathway

BackgroundOsteoporosis (OP) is a common metabolic bone disease. Low-intensity pulsed ultrasound (LIPUS) can effectively promote bone formation and fracture healing. The Wnt/β-catenin signaling pathway is crucial for regulating bone homeostasis and bone diseases, and its downregulation is one of the main mechanisms of osteoporosis pathogenesis. Interleukin-11 (IL-11), which is regulated by mechanical stress, is a key factor in bone remodeling. Here, we investigated the optimal intervention parameters for LIPUS, the relationships among LIPUS, IL-11, and the Wnt/β-catenin signaling pathway, and the effects of LIPUS on bone loss and potential molecular mechanisms in ovariectomized (OVX) mice. MethodsBone marrow mesenchymal stromal cells (BMSCs) were subjected to LIPUS intervention for 0, 10, or 20 min to determine the optimal intervention time. The mediating role of IL-11 in LIPUS intervention was explored through IL-11 knockdown and overexpression. Finally, animal experiments were conducted to investigate the in vivo therapeutic effects of LIPUS. ResultsThe optimal intervention time for LIPUS was 20 min. LIPUS promoted IL-11 expression and upregulated the Wnt/β-catenin signaling pathway, thereby promoting osteogenic differentiation and inhibiting adipogenic differentiation of BMSCs. IL-11 mediates the regulation of the Wnt/β-catenin signaling pathway by LIPUS. Additionally, LIPUS effectively improved the bone microstructure in ovariectomized mice, inhibited bone loss, promoted IL-11 expression in bone tissue, and activated the Wnt/β-catenin signaling pathway in the femur. ConclusionLow-intensity pulsed ultrasound can regulate BMSCs differentiation and inhibit bone loss by promoting IL-11 expression and activating the Wnt/β-catenin signaling pathway.

Expression of interleukin-8 and integrin β3 predicts prognosis of patients with hepatocellular carcinoma after hepatectomy.

As important components in the tumor microenvironment, interleukin-8 (IL-8) and integrin β3 play a key role in the progression and metastasis of hepatocellular carcinoma (HCC). This study aimed to determine the expression of IL-8 and integrin β3 and their prognostic value in patients with HCC after hepatectomy. We investigated the expression of IL-8 and integrin β3, their clinical significance, as well as their correlation in the cancer tissue of 130 patients with HCC using immunohistochemistry. The prognostic value of IL-8 and integrin β3 was investigated through the follow-up of patients with HCC after hepatectomy. In HCC, IL-8 expression had a positive correlation with integrin β3 expression. Increased expressions of IL-8 and integrin β3 were indicators of tumor progression and poor prognosis in patients with HCC after hepatectomy. IL-8 positive specimens exhibited a higher proportion of macrovascular invasion, larger tumor size, poor differentiation, and advanced tumor-node-metastasis (TNM) stage (P < .05, respectively). Integrin β3 positive group exhibited a higher proportion of TNM III-staged tumors (P < .05). The results indicated that macrovascular invasion, advanced TNM stage, and integrin β3 expression were independent unfavorable prognostic factors in HCC after hepatectomy. Integrin β3 expression was proved to be an independent unfavorable prognostic factor in HCC after hepatectomy. Targeting integrin β3 might be a potential therapeutic approach in preventing tumor progression in HCC.

Ginseng fruit rare saponins (GFRS) improved inflammatory response: In vitro and in vivo assessment

Inflammation is the body's protective immune response to tissue damage. Ginseng has a long history of medicinal use, and its active ingredient ginsenosides have anti-inflammatory effects. Ginseng fruit rare saponins (GFRS) is a transformation product of ginseng saponins and rich in a variety of rare saponins. We used HPLC-DAD method to study GFRS rare saponins with ginsenoside F4, R-Rg3, SRg3, Rk1, Rg6, Rg5, Rk3 and Rh4. However, there is no study on the use of GFRS to reduce skin inflammation. This study enriched the action pathway of GFRS through network pharmacology and revealed the anti-inflammatory effect of GFRS for the first time. In vitro experiments showed that GFRS could significantly reduce the release of NO in lipopolysaccharide (LPS) -induced RAW264.7 cells and HaCaT cells, and reduce the secretion and expression of inflammation-related factors Interleukin-6 (IL-6), Tumor necrosis factor-α (TNF-α) and Interleukin-17 A (IL-17 A), thereby reducing cell inflammatory damage. In the imiquimod (IMQ) -induced mouse inflammatory model, the therapeutic effect of GFRS on the pathogenesis of psoriasis-like dermatitis was studied. In vivo experiments showed that the skin erythema, scales, thickness and inflammatory infiltration of GFRS-treated mice were reduced, and the psoriasis area severity index score was significantly lower than that of IMQ group. GFRS restored IMQ-induced spleen size and reduced the secretion and expression of TNF-α, IL-6, Interferon-γ (IFN-γ) and IL-17 A in serum. In summary, our results demonstrate that GFRS alleviates IMQ-induced dermatitis symptoms, effectively reduces the secretion of inflammatory factors, and inhibits IL-17 A expression.

Use of Nuclear Factor of Activated T Cell-Regulated Gene Expression for Monitoring Immunosuppression with Extended-Release Tacrolimus after Liver Transplantation-A Proof of Concept.

There is a narrow therapeutic window for immunosuppression using calcineurin inhibitors. Drug trough levels do not reflect immunosuppression and should be replaced by pharmacodynamic monitoring. This prospective cohort study was designed to evaluate the effect of an extended-release formulation of tacrolimus (LCP Tac) on the nuclear factor of activated T cell-regulated gene expression (NFAT-RGE). The expression of interleukin-2, interferon-γ, granulocyte-macrophage colony-stimulating factor, and three reference genes was measured. Samples from 23 patients at defined time points in the first year after liver transplantation were analyzed using a droplet digital polymerase chain reaction. All samples were within the targeted trough levels of LCP Tac, and their LCP Tac peak levels and residual NFAT-RGE showed a strong inverse correlation (r = -0.8). Most importantly, there was an individual immunosuppressive response to the LCP Tac. The mean individual trough effect of LCP Tac on the three target genes when all time points were pooled was 33% (26-56%) in patients without infection and 81% (53-95%) in those with infection (p < 0.011). The mean individual peak effect was 48% (44-64%) in patients without infection and 91% (90-94%) in those with infection (p < 0.001). Thus, tailored immunosuppression based on residual NFAT-RGE could prevent infections associated with over-immunosuppression early after liver transplantation.

Regulation of the NF-κB/NLRP3 signalling pathway by Shenghui Yizhi decoction reduces neuroinflammation in mice with Alzheimer’s disease

Background Shenghui Yizhi Decoction (SHYZD) has exhibited the capacity to enhance cognitive function and learning abilities in individuals diagnosed with Alzheimer’s disease (AD) while ameliorating pre-existing neuroinflammation. Nevertheless, the precise mechanism underlying its therapeutic effects on AD remains to be elucidated. Methods Twenty-four male SAMP8 mice were randomly divided into three groups, and eight male SAMR1 mice were used as a blank control, to examine their learning and spatial memory abilities. The expression of amyloid β1-42 (Aβ1-42) was detected by immunohistochemical staining of hippocampal tissue. ELISA was used to detect the interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) expressions. Real time PCR was used to detect NOD-like receptor thermal protein domain associated protein 3 (NLRP3), cysteine protease-1 (Caspase-1), and IL-1β mRNA expression. Western blot was used to detect nuclear factor kappa-B (NF-κB), inhibitor of NF-κB α (IκBα), IκB kinase α (IKKα), NLRP3, Caspase-1, and IL-1β protein expression. Results In this study, SAMP8 mice, employed as an AD model, displayed markedly diminished abilities in terms of spatial localization, navigation, and spatial exploration when compared to the blank control group. Additionally, there was a substantial upregulation of Aβ1-42 expression in the hippocampus of these mice, along with a significant increase in the levels of inflammation-associated factors, including IL-1β, IL-6, TNF-α, NLRP3, Caspase-1, as well as the NF-κB pathway-related proteins, namely, NF-κB, IκBα, and IKKα. Moreover, after treatment with positive drugs (donepezil hydrochloride) and SHYZD, the learning abilities of the mice exhibited significant improvements. Furthermore, the hallmark AD protein Aβ1-42, inflammatory factors, and NF-κB/NLRP3 signalling pathway proteins were significantly reduced. These findings collectively suggest that SHYZD exerts a therapeutic effect on AD. Conclusion In summary, the specific molecular mechanisms through which SHYZD alleviates AD and the potential role for SHYZD in the NF-κB/NLRP3 signalling pathway are identified in this study.

The lasso peptide produced by Bacillus licheniformis MCC 2514 demonstrates efficacy in treating in-vivoSalmonella Typhimurium infection

Salmonella, a significant pathogen transmitted through food, presents a substantial threat to public health. The issue of antibiotic misuse is causing a quest for alternative replacements. An antimicrobial peptide, predicted as lasso peptide 2514 (LP-2514), derived from the probiotic bacteria Bacillus licheniformis MCC 2514, has demonstrated effectiveness against various foodborne pathogens including Salmonella. This study aims to assess the efficacy of this peptide in vivo. Mice infected with Salmonella Typhimurium received daily oral administration of LP-2514 (30 mg/kg/day) for 2 weeks until the symptoms subsided. After the treatment, biochemical and histopathological parameters were examined. LP-2514 treated mice demonstrated reduced infection, as evidenced by a 5-fold decrease in aspartate aminotransferase concentration and a 10-fold decrease in alanine aminotransferase concentration in plasma. Nitric oxide generation was decreased by 61.23 %, C-reactive protein by 75.9 %, and numerous antioxidant enzymes were elevated to suppress the infection. Increased expression of the anti-inflammatory marker Interleukin-10 (IL-10) by 43-fold was observed in treated mice, while untreated mice displayed elevated expression of pro-inflammatory cytokines indicating the severity of infection. Hence, LP-2514 successfully alleviated the disease symptoms caused by S. Typhimurium, thus exhibiting as a potential replacement for antibiotics or food-grade preservatives.

Comparative Analysis of Corneal Wound Healing: Differential Molecular Responses in Tears Following PRK, FS-LASIK, and SMILE Procedures.

In this study, we aimed to analyze the changes in the expression profiles of selected messenger RNAs (mRNAs) and their encoded proteins in the tears of patients undergoing photorefractive keratectomy (PRK), femtosecond-assisted laser in situ keratomileusis (FS-LASIK), and small-incision lenticule extraction (SMILE) procedures. A total of 120 patients were divided into three groups based on the laser vision correction (LVC) procedure: PRK, FS-LASIK, or SMILE. Tear samples were collected preoperatively and at 1, 7, 30, and 180 days postoperatively. The expression levels of selected messenger RNAs (mRNAs) and proteins were analyzed by using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA), respectively. PRK and FS-LASIK elicited significantly stronger biological responses than SMILE. Interleukin-15 (IL-15) expression increased notably in the PRK and FS-LASIK groups, with mRNA levels reaching fold changes of 4.65 ± 0.65 and 4.99 ± 0.28, respectively, on day 1, compared with only 2.09 ± 0.23 in the SMILE group. Vascular endothelial growth factor A (VEGFA) levels were also elevated in the PRK (2.98 ± 0.23 fold change) and FS-LASIK groups (3.45 ± 1.09 fold change) on day 1, while the SMILE group showed minimal fluctuations. The protein concentration analysis based on the ELISA confirmed these trends, with IL-15 levels peaking at 54.2 ± 2.5 pg/mL in the PRK group and 52.8 ± 3.1 pg/mL in the FS-LASIK group, compared with 32.4 ± 1.9 pg/mL in the SMILE group on day 1. Similarly, VEGFA protein concentrations were the highest in the PRK (72.4 ± 4.1 pg/mL) and FS-LASIK patients (69.5 ± 3.8 pg/mL) on day 1 but remained low in the SMILE patients (45.6 ± 2.3 pg/mL). By day 180, gene expression and protein levels in all groups had stabilized, returning to near-preoperative values. PRK and FS-LASIK induced more pronounced molecular and protein-level changes during corneal wound healing than the less invasive SMILE procedure, indicating stronger biological responses. These findings suggest that tailored postoperative care based on the specific procedure could optimize healing and patient outcomes. However, further research with larger sample sizes and longer follow-ups is needed to confirm these observations and develop personalized treatment strategies.

Effect of curcumin and cacao extract on interleukin-6 expression on ribociclib-induced hepatotoxicity in rats

Purpose: To assess the relationship between interleukin-6 (IL-6) expression and the protective effect of curcumin and cacao extract on hepatotoxicity caused by ribociclib. Method: Sixty adult male albino rats (9 – 10 weeks old) were utilized in this experiment. The rats were separated into six groups (n = 10 each). Group 1 (control) rats received 2 mL of normal saline daily. Group 2 rats were administered 5 mg/kg ribociclib and group 3 rats received 5 mg/kg ribociclib with a cacao dose of 200 mg/kg daily. Group 4 rats were administered 5 mg/kg ribociclib treated with curcumin (200 mg/kg) daily. Groups 5 and 6 were administered cacao and curcumin doses of 200 mg/kg daily. All rats were sacrificed and liver immunohistochemical and histological examinations were performed. Result: The findings demonstrated that ribociclib administration caused liver damage and morphological changes at a histological level in liver tissue. The immunohistochemical investigation revealed that IL-6 levels were significantly increased in group 2 and control group (p &lt; 0.05). Furthermore, co-administration of curcumin and cacao with ribociclib suppressed the levels of IL-6 expression in the liver tissue of rats compared to control group 1. Conclusion: Co-administration of curcumin and cacao protects the liver against ribociclib-induced liver damage. It is necessary to determine the effect of long-term administration of these extracts on the functions of some organs such as the liver and kidney.

Lactoferrin modulates oxidative stress and inflammatory cytokines in a murine model of dysbiosis induced by clindamycin.

Antibiotics, specifically clindamycin, cause intestinal dysbiosis, reducing the microbiota with anti-inflammatory properties. Furthermore, clindamycin can induce alterations in the immune responses and oxidative stress. Lactoferrin, among other activities, participates in the maintenance of intestinal homeostasis and reduces dysbiosis induced by antibiotic treatment. The aim of this study was to analyze the effect of native and iron-saturated bovine LF in a murine model of dysbiosis induced by clindamycin. Six groups of male C57BL/6 mice were treated with saline (control), clindamycin (Clin), native lactoferrin (nLF), iron-saturated lactoferrin (sLF), nLF/Clin or sLF/Clin. Oxidation caused in the intestinal cells of the ileum of animals subjected to different treatments was analyzed, focusing on lipid peroxidation and protein carbonyl content. The expression of inflammatory mediators was determined by qRT-PCR. Treatment with clindamycin did not modify lipid peroxidation, but significantly increased protein carbonyl levels up to almost 5-fold respect to the control, an effect that was reversed by orally administering sLF to mice. Furthermore, clindamycin increased the expression of interleukin-6 and TNF-α by 1- and 2-fold change, respectively. This effect was reversed by treatment with nLF and sLF, decreasing the expression to basal levels. In conclusion, this study indicates that lactoferrin can prevent some of the effects of clindamycin on intestinal cells and their associated immune system.

Detection and Localization of IL-8 and CXCR1 in Rainbow Trout Larvae in Response to Pseudomonas aeruginosa Lipopolysaccharide

The salmonid industry faces challenges due to the susceptibility of fish to opportunistic pathogens, particularly in early developmental stages. Understanding the immunological capacity during these stages is crucial for developing effective disease control strategies. IL-8R, a member of the G-protein-coupled receptor family, acts as a receptor for Interleukin 8 (IL-8). The binding of IL-8 to IL-8R plays a major role in the pathophysiology of a wide spectrum of inflammatory conditions. This study focused on the immune response capacity of rainbow trout (Oncorhynchus mykiss) larvae by analyzing IL-8/CXCR1 response to lipopolysaccharide (LPS) from Pseudomonas aeruginosa. Previous research demonstrated that LPS from P. aeruginosa acts as a potent immunostimulant in teleost, enhancing pro-inflammatory cytokines. The methodology included in silico analysis and the synthesis and characterization of an omCXCR1-derived epitope peptide, which was used to produce omCXCR1-specific anti98 serum in mice. The research revealed that rainbow trout larvae 19 days post-hatching (dph) exhibited pronounced immune responses post-stimulation with 1 µg/mL of LPS. This was evidenced by the upregulated protein expression of IL-8 and omCXCR1 in trout larvae 2 and 8 h after LPS challenge, as analyzed by ELISA and immunohistochemistry. Furthermore, fluorescence microscopy successfully revealed the colocalization of IL-8 and its receptor in cells from mucosal tissues after LPS challenge in larvae 19 dph. These findings underscore the efficacy of LPS immersion as a method to activate the innate immune system in trout larvae. Furthermore, we propose IL-8 and its receptor as molecular markers for evaluating immunostimulation in the early developmental stages of salmonids.

Dietary glutamine supplementation improves both Th1 and Th17 responses via CARD11-mTORC1 pathway in murine model of atopic dermatitis

Glutamine (GLN) is considered an immunomodulatory nutrient, while caspase recruitment domain 11 (CARD11) is a susceptibility locus for atopic dermatitis (AD). T-cell antigen receptor (TCR)-stimulated GLN uptake requires CARD11. However, the specific pathogenesis of AD via GLN uptake remains unclear. This study aimed to elucidate the association between dietary GLN supplementation and the CARD11 pathway in the pathogenesis of AD, focusing on T helper type 1 (Th1) and Th17 cell expression in AD. Herein, wild-type (WT) mice with house dust mite epidermal-sensitized skin exhibited increased expression of interferon-gamma (IFN-gamma) and interleukin (IL)-17, whereas CARD11 deficiency impaired Th1 and Th17 responses at the same site. CARD11 is a key mediator of Th1 and Th17 expression in AD. Additionally, we suppressed mammalian target of rapamycin complex 1 (mTORC1) signaling, downstream of CARD11, to underscore the critical role of CARD11 in mediating Th1 and Th17 expression in AD. Further, dietary supplementation of GLN to CARD11−/− mice restored Th1 and Th17 responses, whereas inflammatory expression was reduced in WT mice, and p-CARD11 expression and mTORC1 signaling activity were increased in JPM50.6 cells and CARD11−/− mice. Upon inhibiting the GLN transporter, alanine-serine-cysteine transporter carrier 2 (ASCT2), we observed that the Th1 and Th17 response in AD was reduced. Conclusively, ASCT2-mediated GLN uptake improves the expression of Th1 and Th17 cells via CARD11-mTORC1 signaling pathway in AD, suggesting the potential of glutamine supplementation for AD treatment.

Chromofungin mitigates free fatty acids-induced endothelial inflammation via inhibition of NOD-like receptor thermal protein domain-associated protein 3 mediated by adenosine 5'-monophosphate-activated protein kinase.

Free fatty acids (FFAs) have emerged as significant risk factors for atherosclerosis (AS). Prolonged exposure to FFAs induces vascular endothelial injury, including inflammatory responses and oxidative stress, which are central events in AS. Chromofungin (CHR), a peptide derived from chromogranin A (CGA), has been implicated in various biological functions. However, its physiological roles in endothelial biology and its involvement in the pathological development of AS have not been previously reported. In the present study, we investigated the underlying mechanisms through which CHR exerts its beneficial effects on FFA-challenged human aortic endothelial cells (HAECs). We found that treatment with CHR ameliorated the FFA-induced reduction in cell viability and increase in lactate dehydrogenase (LDH) release. Additionally, CHR mitigated oxidative stress by reducing mitochondrial reactive oxygen species (ROS) levels and increasing superoxide dismutase (SOD) activity. Furthermore, exposure to FFAs increased NADPH oxidase (NOX) 4 expression at both the mRNA and protein levels, which were attenuated by CHR in a dose-dependent manner. Notably, CHR reduced the levels of nucleotide-binding domain and leucine-rich repeat-containing (NLR) family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), and cleaved caspase-1 (p10), key components of the NLRP3 inflammasome complex, as well as interleukin 1β (IL-1β) and interleukin-18 (IL-18) expression. Mechanistically, it was demonstrated that FFAs reduced the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC), which were rescued by CHR in a dose-dependent manner. Conversely, inhibition of AMPK with its specific inhibitor compound C abolished the protective effects of CHR against FFA-induced activation of the NLRP3 inflammasome in HAECs. Based on these findings, we conclude that CHR may serve as a promising agent for maintaining normal endothelial cell function and treating AS.

Emerging Roles of IL-27 in Trophoblast Cells and Pregnancy Complications.

Pregnancy complications such as spontaneous abortion, preeclampsia, and preterm birth persist, despite current interventions aimed at their prevention and treatment largely proving unsuccessful. Interleukin-27 (IL-27), composed of p28 and EBI3 subunits, binds to IL-27R, which consists of gp130 and IL-27Rα (also known as WSX-1 or TCCR), and plays a pivotal role in tumor development and inflammation regulation. At the maternal-fetal interface, IL-27 expression has been detected in trophoblasts, endometrial stromal cells, and decidual cells. Abnormal levels of IL-27/IL-27R have been linked to adverse pregnancy outcomes, including spontaneous miscarriage, preeclampsia, and preterm birth. This review aims to explore the expression of IL-27 at the maternal-fetal interface and its signaling pathway, uncovering the complex role of IL-27 in pregnancy complications. A comprehensive literature review was conducted using PubMed/Medline, Scopus, and Embase databases, analyzing studies on IL-27 expression and its signaling pathways at the maternal-fetal interface. The review focused on identifying the presence of IL-27 in various cell types and linking abnormal IL-27/IL-27R expression to pregnancy complications such as spontaneous miscarriage, preeclampsia, and preterm birth. IL-27 plays a complex role at the maternal-fetal interface, with abnormal expression linked to several pregnancy complications. These findings highlight the need for further research to elucidate IL-27's mechanisms and develop targeted interventions. Future studies should aim to develop targeted interventions and improve therapeutic strategies for managing pregnancy complications.

Mesenchymal stem cells suppress inflammation by downregulating interleukin-6 expression in intestinal perforation animal model

Introduction: Intestinal perforation has significant fatality due to sepsis contamination and prolonged inflammation. Studies showed that mesenchymal stem cells (MSCs) secreted cytokines and growth factors to reduce inflammation. This study aims to reveal the role of MSCs in controlling inflammation in intestinal perforation wound healing by measuring interleukin-6 (IL-6) and leukocytes in injured tissue. Materials and methods: A total of 48 rat models with a 10-mm longitudinal incision at the small intestine were divided into four groups: sham, control, Treatment group 1 (T1) injected with MSC doses of 1.5×106 cells and Treatment group 2 (T2) with 3×106 cells. IL-6 expressions were determined using western blot analysis, whereas the leukocyte infiltrations were assessed using the histopathological examination. All variables were evaluated on day 3 and 7. Results: Leukocyte infiltration is significantly lower in T1 and T2 compared to control group in day 3 and 7 (P&lt;0.05), while there were no differences between the two treatment groups. The expression of IL-6 was found to be significantly lower in the T1 and T2 groups compared to the control group on days 3 and 7 (P&lt;0.05), with no significant differences observed between the two treatment groups. Conclusion: MSCs administration in rats with intestinal perforation reduced inflammation by controlling leukocyte infiltration and IL-6 expression.