Serum interleukin-17A Levels Research Articles

Investigation of IL-17A Serum Levels in Patients with Nonmelanoma Skin Cancer.

Background Role of interleukin 17A (IL-17A) in carcinogenesis and cancer growth is controversial. Although some researches support its antitumor activity, some others suggest that it promotes the growth and development of different types of cancer including skin cancer by activation of STAT3. Although the function of the cytokines such as IL-17A has been extensively studied in various types of cancer, nonmelanoma skin cancer (NMSC) has not received much attention. Therefore, the present study was aimed to investigate the serum levels of IL-17A in NMSC patients. Methods This cross-sectional study was performed on 60 patients with basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) as well as 57 age-sex matched healthy individuals as control group. Measurement of IL-17A serum levels in both case and control groups was performed by a commercially reliable sandwich enzyme-linked immunosorbent assay (ELISA) kit. Results In this study, we observed that IL-17A serum levels in NMSC patients were significantly higher than the control group (P < 0.001). Also, both BCC and SCC patients had higher levels of IL-17A in their sera in comparison to the controls (P=0.001 and P < 0.001, respectively). However, there was no significant difference between SCC and BCC patients regarding serum levels of IL-17A. Conclusion According to our results, it can be concluded that IL-17A may play a role in inducing the growth and progression of NMSC and it can be used as a therapeutic target in these patients in future.

IL-17A and CCL2 in blood serum and circulating neutrophils in patients with ovarian tumors.

e17536 Background: During the ovarian carcinogenesis, circulating neutrophils (Nph) phenotype switches to the pro-tumor, with an increase in the Nph C-C motif ligand 2 (CCL2) expression. Proinflammatory interleukin-17A (IL-17A) is able to induce the CCL2 expression in Nph. The study aimed to evaluate the IL-17A and CCL2 levels in serum and circulating Nph in patients with ovarian tumors. Methods: The study included 97 ovarian cancer (OC) patients, 30 patients with benign ovarian tumors (BT) and the control (n=22). The levels of IL-17A (LLC "Cytokine", Russia) and CCL2 (Vector-Best-Volga, Russia) in serum and Nph lysate were assessed by ELISA. The systemic inflammation was assessed by neutrophil to lymphocyte ratio (NLR). Informed voluntary consent was obtained from all women. Statistical processing was performed using one-way ANOVA, Spearman correlations (Statistica 13.0 (TIBCO, USA)). Results: We found an increase in NLR in BT (4.3 ± 1.0) compared with the control (2.2 ± 0.1) (p = 0.020), a decrease in stage I-II OC (2.4 ± 0.2) compared with BT (p = 0.053), and an increase in stage III (4.5 ± 0.9) and IV (4.6 ± 0.5) compared with stage I-II OC (p = 0.054 and p = 0.046, respectively). The cytokines levels are presented in Table. The serum level of IL-17A in BT was higher than in the control (p = 0.010). In stage I-II OC, the serum IL-17A level was decreased in comparison with the BT (p = 0.004). In stage IV OC, the serum IL-17A was higher than in stage I-II (p = 0.015) and the control (p = 0.017). The level of IL-17A in Nph in BT did not differ from the control. In all stages of the OC, the IL-17A Nph level was lower than in the control (p1, 2, 3 = 0.0001). In stage IV OC, the expression of IL-17A in Nph was lower compared with stage III (p = 0.031). The serum and Nph levels of IL-17A were correlated only in stage I-II OC (r = 0.679, p = 0.011). The CCL2 serum levels in BT (p = 0.0002) and OC stage I-II, III, IV were higher compared with the control (p1 = 0.031, p2 = 0.001, p3 = 0.0005, respectively). The Nph CCL2 level was higher in BT than in the control (p = 0.001). In stage I-II OC, the expression of CCL2 in Nph was higher than in the control (p = 0.034), but lower than in the BT (p = 0.003). In OC stages III and IV, the Nph CCL2 level was higher than in the control, but did not differ from that in BT and stages I-II. In stage III OC, the CCL2 level in Nph negatively correlated with the serum IL-17A level (r = -0.405, p = 0.049). Conclusions: The pro-tumor polarization of circulating Nph is not IL-17A-dependent in patients with ovarian tumors. The patterns of the systemic immune response differ in benign ovarian tumors, early, and advanced ovarian cancer.[Table: see text]

Dyslipidemia among allergic rhinitis patients: Frequency and risk factors

BackgroundAlthough cumulative data strongly suggest an association between dyslipidemia and allergic disorders, especially asthma, evidence regarding allergic rhinitis (AR) is lacking. We aimed to assess frequency and associated risk factors of dyslipidemia among patients with AR. MethodsThe current study is a cross-sectional study that recruited 150 AR patients by systematic randomization. Blood samples for serum lipid profile, total immunoglobulin E (IgE) and serum interleukin-17A (IL-17A) were withdrawn from all patients. ResultsDyslipidemia was prevalent in 84 AR patients (56%). Higher levels of total IgE, IL17-A, and sensitization to hay dust and mixed mites significantly increased the risk of dyslipidemia among AR patients by 1.004, 1.062, 4.057 and 3.652 respectively (P < 0.05). ConclusionHigh serum total IgE level, high serum IL-17A level, and sensitization to hay dust and mixed mites are independent risk factors for dyslipidemia among AR patients.

Serum interleukin-17A level after on-pump coronary artery bypass grafting surgery

Serum interleukin-17A level after on-pump coronary artery bypass grafting surgery

A Novel Selective Sphingosine Kinase 2 Inhibitor, HWG-35D, Ameliorates the Severity of Imiquimod-Induced Psoriasis Model by Blocking Th17 Differentiation of Naïve CD4 T Lymphocytes.

Sphingosine kinases (SK) catalyze the phosphorylation of sphingosine to generate sphingosine-1-phosphate. Two isoforms of SK (SK1 and SK2) exist in mammals. Previously, we showed the beneficial effects of SK2 inhibition, using ABC294640, in a psoriasis mouse model. However, ABC294640 also induces the degradation of SK1 and dihydroceramide desaturase 1 (DES1). Considering these additional effects of ABC294640, we re-examined the efficacy of SK2 inhibition in an IMQ-induced psoriasis mouse model using a novel SK2 inhibitor, HWG-35D, which exhibits nM potency and 100-fold selectivity for SK2 over SK1. Topical application of HWG-35D ameliorated IMQ-induced skin lesions and normalized the serum interleukin-17A levels elevated by IMQ. Application of HWG-35D also decreased skin mRNA levels of interleukin-17A, K6 and K16 genes induced by IMQ. Consistent with the previous data using ABC294640, HWG-35D also blocked T helper type 17 differentiation of naïve CD4+ T cells with concomitant reduction of SOCS1. Importantly, HWG-35D did not affect SK1 or DES1 expression levels. These results reaffirm an important role of SK2 in the T helper type 17 response and suggest that highly selective and potent SK2 inhibitors such as HWG-35D might be of therapeutic use for the treatment of psoriasis.

Elevated Levels of Serum IL-17A Secondary to Repeated Intravitreal Injections of Aflibercept in Treatment-Naive Patients with Neovascular Age-Related Macular Degeneration

We evaluated the effect of three monthly intravitreal injections of aflibercept on the serum concentration of interleukin 17A (IL-17A), monocyte chemoattractant protein 1 (MCP-1/CCL2), vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) in treatment-naive patients with neovascular age-related macular degeneration (nAMD). Twenty-two eyes of twenty-two patients with nAMD scheduled for the initial loading phase of intravitreal aflibercept (2 mg/0.05 mL) were included. Serum VEGF, PlGF, MCP-1/CCL2 and IL-17A levels were determined four times in each individual—just before the first injection, 2–3 days after the first injection, just before the third injection, and then 2–3 days after the third aflibercept injection. A statistically significant difference was found between the serum PlGF and IL-17A levels measured before the first injection and after the initial loading phase, with a mean value (MV) of 440.884 vs. 302.151 (p = 0.023) for PlGF and MV = 139.088 pg/mL vs. 151.233 pg/mL (p = 0.016) for IL-17A, respectively. There were no statistically significant differences for VEGF and MCP-1/CCL2 between any of the compared measurements. We reveal that repeated injections of aflibercept promote an increase in serum IL-17A concentration, which may lead to a systemic inflammatory response mediated by IL-17A, but not by MCP-1.

The Role of Highly Active Antiretroviral Therapy (HAART) on Interleukin 17A (IL-17A) in Normotensive and Preeclamptic Black South African Women.

Introduction Interleukin 17A has been implicated in the pathophysiology of both human immune deficiency virus and preeclampsia. This study evaluated serum levels of IL-17A based on pregnancy type, gestational age, HIV status, and duration of HAART. Material and Methods. A sample size of 250 was analysed: normotensives (n = 150; N) and preeclamptics (n = 100; PE). Normotensives were further stratified into HIV negative (n = 90), HAART-acute (n = 30), and HAART-chronic (n = 30). The PE group was divided into early onset (n = 50; EOPE) and late onset (n = 50; LOPE). The EOPE and LOPE groups were subdivided into HIV negative (n = 30), HAART-acute (n = 10), and HAART-chronic (n = 10). Analysis of IL-17A was performed using a multiple Bio-Plex immunoassay method. Results Pregnancy type: the levels of IL-17A were increased in PE compared to N (P = 0.0014). Gestational age: the levels of IL-17A were increased in EOPE compared to N group (P = 0.0113). A significant increase in the levels of IL-17A in LOPE compared to N was observed (P = 0.0063). HIV status: the levels of IL-17A were increased in PE compared to N (P = 0.0114) and in EOPE compared to N groups (P = 0.0071). HAART duration: the concentration of IL-17A was increased in HAART-chronic PE compared to N groups (P = 0.0062). There was also an increase in the levels of IL-17A in EOPE compared to N (P = 0.0029). Conclusion The study demonstrates that IL-17A is involved in the pathophysiology of PE and that in the presence of HIV infection, chronic HAART administration predisposes women to the development of EOPE.

Low Serum IL-17A in Pregnancy During Second Trimester Is Associated With an Increased Risk of Subclinical Hypothyroidism

Problem: Interleukin-17A (IL-17A) has a role in sustaining normal pregnancy. IL-17A is also associated with thyroid autoimmunity during pregnancy. This study sought to investigate whether IL-17A is a risk factor for thyroid dysfunction during pregnancy in women negative for thyroid autoantibodies.Methods of Study: The study comprised 216 pregnant women with negative thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb) during the second trimester who provided blood samples for serum IL-17A, thyroid autoantibodies and thyroid function tests. To further evaluate the ratio of CD4+IL-17A+ Th17 cells, we collected peripheral blood from 26 women with thyroid-stimulating hormone (TSH) levels ≤ 2.5 mIU/L and 26 pregnancy-week matched women with TSH levels >2.5 mIU/L, along with samples from 20 women with TSH levels ≤ 4 mIU/L and 20 pregnancy-week matched women with TSH levels >4 mIU/L.Results: The serum IL-17A levels and ratios of CD4+IL-17A+ cells were significantly lower in women with TSH > 2.5 mIU/L than in those with TSH ≤ 2.5 mIU/L (both P < 0.01). Similar lower differences were noted in women with TSH > 4 mIU/L than in those with TSH ≤ 4 mIU/L (both P < 0.01). Moreover, serum TSH correlated negatively with IL-17A levels (β = −0.195, P = 0.004), but positively with the week of gestation (β = 0.284, P < 0.001). Logistic regression indicated that a lower serum IL-17A level was a risk factor for TSH > 2.5 mIU/L [OR = 0.453 (0.298–0.689), P = 0.000] and TSH > 4.0 mIU/L [OR = 0.588 (0.385–0.899), P = 0.013].Conclusion: A low serum IL-17A level during the second trimester is associated with an increased risk of TSH > 2.5 mIU/L and subclinical hypothyroidism.

Association of interleukin-17A gene polymorphisms and susceptibility to systemic lupus erythematosus in Egyptian children and adolescents: a multi-centre study.

Recently, the interleukin-17A (IL-17A) gene has emerged as a potential candidate gene for autoimmune disorders, including systemic lupus erythematosus (SLE). This study aimed to investigate whether IL-17A polymorphisms at rs2275913 G/A, rs8193036 C/T and rs3748067 C/T could be susceptibility markers for juvenile-onset SLE (JSLE) and lupus nephritis (LN) in Egyptian children and adolescents. In this multi-centre study, we genotyped 320 patients diagnosed with JSLE and 320 matched control children for three IL-17A polymorphisms at rs2275913 G/A, rs8193036 C/T and rs3748067 C/T using TaqMan probe-based real-time polymerase chain reaction. Meanwhile, IL-17A serum levels were assessed using ELISA. The IL-17 rs2275913 A/A genotype and A allele were more represented in JSLE patients compared to the control group (21% vs. 7%, odds ratio (OR) = 3.8, 95% confidence interval (CI) 1.78-5.5, p = 0.001, pBonf = 0.003 for the A/A genotype; 37% vs. 29%, OR = 1.4, 95% CI 1.11-1.8, p = 0.003, pBonf = 0.009 for the A allele. No significant difference was found for IL-17 rs8193036 and rs3748067 single nucleotide polymorphisms (SNPs) in genotype distribution or allele frequencies (p>0.05). Patients carrying the IL-17 rs2275913 A/A genotype and A allele were more likely to develop LN (OR = 5.64, 95% CI 2.39-13.77, pBonf = 0.001 for the A/A genotype; OR = 2.73, 95% CI 1.84-4.07, pBonf = 0.02 for the A allele). The IL-17 rs2275913 A allele and A/A genotype were associated with high IL-17 serum levels and may contribute to susceptibility to JSLE and the development of LN in Egyptian children and adolescents. However, no significant association was evident between the studied IL-17A SNPs and other clinical phenotypes, disease activity scores or laboratory profile of JSLE.

Association study between rs2275913 genetic polymorphism and serum levels of IL-17A with risk of coronary artery disease.

Coronary artery disease (CAD) is now considered as a main cause of disability and mortality in Iranian population. Inflammatory processes are the initial events in the development of CAD. Interleukin-17A (IL-17A) is a pro-inflammatory cytokine and its genetic variation may contribute to the development of CAD. This study investigated serum levels and the G-197A polymorphism of IL17A in a group of patients with CAD and healthy controls. The study population included 220 angiographically verified CAD patients and 220 healthy controls. Genotyping of G-197A polymorphism of IL17A was done by PCR-RFLP method and serum level of IL-17 was measured by enzyme immunoassay. Results indicated that serum concentration of IL-17A was significantly higher in CAD group than control group (P<0.001). Also, serum levels of IL-17A was significantly higher in carriers of GA and AA genotype relative to carriers of GG genotype in both study population (P<0.05). The G-197A polymorphism of IL17A increased the risk of CAD in mutant homozygous (P=0.007) but not heterozygous (P=0.104) genotype. Moreover, this polymorphism was associated with higher risk of CAD development in allelic (P=0.041) model. However, no significant association was observed between genotypic distribution of G-197A polymorphism and the number of stenotic vessels (P>0.05). In conclusion, the present study indicated G-197A polymorphism of IL17A as a significant contributor to the development but not to the severity of CAD. Moreover, elevated serum levels of IL-17A were identified as a susceptibility marker of CAD.

Fortum to acquire Crisolteq, a recycling specialist of valuable metals in batteries

Interleukin-17A (IL-17A) has been implicated in the pathogenesis of viral myocarditis (VMC). However, the role of IL-17A polymorphisms in susceptibility to VMC has not been reported to date. The aim of this study was to explore the association between IL-17A variants as well as serum IL-17 levels with VMC. Three single-nucleotide polymorphisms (SNPs) (rs2275913, rs3819025, and rs3748067) were analyzed by the polymerase chain reaction-restriction fragment length polymorphism method in 236 VMC patients and 259 controls from China. Serum IL-17A levels were measured by enzyme-linked immunosorbent assay kits. Multivariable logistic regression analysis that the rs2275913 AA genotype and the haplotype -197A/+45G/+1249G (AGG) were associated with an increased risk of VMC (all P < 0.05). Consistent with these findings, the rs2275913 AA genotype was linked to higher serum IL-17A compared to GG/AG genotype (all P < 0.001). We observed no associations between the other two SNPs and risk of VMC. Serum IL-17A levels were significantly higher in the VMC group than controls (P < 0.001) and gradually increased with the increase of New York Heart Association grade in VMC patients (P < 0.05). Spearman correlation test revealed that the serum IL-17A level was correlated with the cardiac damage and left ventricular systolic functions among VMC patients (all P < 0.05). Our study reveals that IL-17A expression may contribute to the development and severity of VMC. The SNP rs2275913 in the IL-17A gene might exert influence on susceptibility to VMC via linking with the serum IL-17A level.

AB004. The role of highly active antiretroviral therapy (HAART) on interleukin 17a (il-17a) in normotensive and pre-eclamptic black South African women

Background: Interleukin 17-A (IL-17A) has been implicated in the pathophysiology of both human immune deficiency virus (HIV) and preeclampsia (PE). This study evaluated serum levels of IL-17A in HIV-negative and HIV-positive normotensive and preeclamptic women receiving highly active anti -retroviral therapy (HAART).

Interleukin 17A promotes gallbladder cancer invasiveness via ERK/NF-κB signal pathway mediated epithelial-to-mesenchymal transition.

As a pro-inflammatory cytokine, Interleukin 17A (IL-17A) plays an important role in pathology of tumor microenvironment and inflammatory diseases. In this study, we intend to investigate the role of IL-17A on the metastasis of gallbladder cancer (GBC) and related mechanisms. The serum levels of IL-17A were associated with node metastasis and advanced stage. We also found the pro-invasion effect of IL-17A on GBC cells. When treated with IL-17A, the protein level of epithelial marker E-cadherin in GBC cells was significantly down-regulated, while the protein level of the mesenchymal phenotype marker vimentin was significantly increased. IL-17A increased the expression of transcription factor slug, the phosphorylation of ERK1/2 and the nuclear translocation of NF-κB/p50 and p65 in a concentration-dependent manner. Pretreatment of cells with U0126 could reverse the nuclear translocation of NF-κB/p50 and p65 and EMT induced by IL-17A. IL-17A promotes gallbladder cancer invasiveness via ERK/NF-κB signal pathway mediated epithelial-to-mesenchymal transition. As a new therapeutic targets and diagnostic marker, IL-17A may play an important role in the treatment of GBC.

Serum and urine interleukin-17A levels as biomarkers of disease activity in systemic lupus erythematosus.

This study examined the correlations of both serum and urine interleukin-17A (IL-17A) levels with disease activity in systemic lupus erythematosus (SLE). This study was also aimed at determining their sensitivity and specificity as biomarkers of disease activity in SLE. A cross-sectional study was performed involving SLE patients (n=120 patients) from Universiti Kebangsaan Malaysia Medical Centre (UKMMC). Serum and urinary IL-17A levels were determined by immunoassay while disease activity was assessed using Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) and British Isles Lupus Assessment Group's 2004 index (BILAG 2004) scores. The correlations between serum and urinary IL-17A levels with total SLEDAI-2K and BILAG 2004 scores were determined using bivariate correlation analyses. Receiver operating characteristic curves were calculated to determine their sensitivity and specificity as disease activity biomarkers. Both serum and urinary IL-17A levels correlated with total scores of BILAG 2004, BILAG renal, BILAG mucocutaneous, and SLEDAI-2K (P<0.05). Urine IL-17A levels correlated positively with urine protein : creatinine index while serum IL-17 level correlated with the BILAG hematology score (all P<0.05). The area under curve of serum IL-17A and urine IL-17A with BILAG and SLEDAI scores were low (<0.75). Despite positive correlations between serum and urine IL-17A with SLE disease activity, both were neither sensitive nor specific as biomarkers to predict active disease. Hence, IL-17 measurement has no role in SLE disease activity assessments and future studies are needed to search for other reliable activity biomarkers.

Association between Interleukin-32 and Interleukin-17A Single Nucleotide Polymorphisms and Serum Levels with Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is correlated with low-grade chronic inflammation. Interleukin-17A (IL-17A) and Interleukin-32 (IL-32) are two members of the pro-inflammatory cytokines which act as significant components of the immune system during certain inflammatory diseases. Along with immunological processes, genetic factors play major roles in predisposition to PCOS. There are myriad single nucleotide polymorphisms (SNPs) within IL-17A and IL-32 genes that may affect their production and the susceptibility of individuals to PCOS. The objective of the present research was to investigate the association between IL-17A (rs2275913) and IL-32 (rs9927163, rs4786370) SNPs, and also their serum levels with susceptibility to PCOS in a group of Iranian women. In this case-control study, 150 PCOS patients (mean age of 29.1 years) and 150 healthy women (mean age of 26.1 years) were analyzed in terms of IL-17A and IL-32 SNPs via polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Furthermore, serum levels of IL-17A and IL-32 cytokines were measured through the use of ELISA method. There were significant differences between PCOS and healthy women regarding IL-17A rs2275913 alleles, genotypes frequencies (p=0.005, and 0.01, respectively) and the allelic distribution of IL-32 rs9927163 SNP (p=0.03). Additionally, significant differences were indicated between two groups concerning the AG genotype against AA+GG genotypes (p=0.009) and the GG genotype against AA+AG genotypes (p=0.006) in IL-17A rs2275913 SNP. In the matter of IL-32 gene SNPs, GC haplotype frequency was significantly different between patients and controls (p=0.05). Furthermore, IL-32 serum level was not significantly different between the two studied groups and the serum level of IL-17A was not detectable. In conclusion, IL-17A and IL-32 SNPs might be associated with predisposition to PCOS in Iranian women.

The Relationship between Epicardial Adipose Tissue Thickness and Serum Interleukin-17a Level in Patients with Isolated Metabolic Syndrome.

In this study, it was aimed to investigate the relationship between the epicardial adipose tissue thickness (EATT) and serum IL-17A level insulin resistance in metabolic syndrome patients. This study enrolled a total of 160 subjects, of whom 80 were consecutive patients who applied to our outpatient clinic and were diagnosed with metabolic syndrome, and the other 80 were consecutive patients who were part of the control group with similar age and demographics in whom the metabolic syndrome was excluded. The metabolic syndrome diagnosis was made according to International Diabetes Federation (IDF)-2005 criteria. EATT was measured with transthoracic echocardiography (TTE) in the subjects. IL-17A serum levels were determined using the ELISA method. Fasting blood glucose, HDL, triglyceride, and fasting insulin levels were significantly higher in the metabolic syndrome group compared to the control group. In addition, the metabolic syndrome group had significantly higher high-sensitivity C-reactive protein (hs-CRP) and Homeostatic Model Assessment Insulin Resistance (HOMA-IR) levels than the control group. Similarly, serum IL-17A levels were significantly elevated in the metabolic syndrome group compared to the control group statistically (p < 0.001). As well, EATT was higher in the metabolic syndrome than the control group. Conclusion: By virtue of their proinflammatory properties, EATT and IL-17 may play an important role in the pathogenesis of the metabolic syndrome.

Pancreatic autoantibodies and CD14+CD16+ monocytes subset are associated with the impairment of ß-cell function after simultaneous pancreas-kidney transplantation.

Pancreatic autoantibodies (AAb) has been associated with a worse pancreas graft survival after simultaneous pancreas-kidney transplantation (SPK). However, due to the variable time for AAb to become positive and the lack of early biomarkers suggesting such autoimmune activation, the mechanisms leading ß-cell destruction remain uncertain. The present study aimed to evaluate the association between post-transplant AAb and the functional impairment of the pancreatic ß-cell and also the association of such AAb with inflammation after SPK. In a longitudinal study, we analyzed the impact of post-transplant glutamic acid decarboxylase (GAD-65) and the insulinoma-associated autoantigen 2 (IA-2) AAb on pancreas graft function. Serum Hb1Ac and C-peptide (C-pep) were longitudinally compared between a group with positive posttransplant AAb (AAb+; n = 40) and another matched group with negative AAb (AAb-; n = 40) until the fifth year following seroconversion. In the cross-sectional analysis, we further evaluated the systemic signatures of inflammation by measuring pro-inflammatory CD14+CD16+ monocytes by flow-cytometry and interleukin 17-A serum levels in 38 SPK recipients and ten healthy controls. In the longitudinal study, patients with AAb+ showed higher levels of Hb1Ac (p<0.001) and lower C-pep levels (p<0.001) compared to those who remained AAb- throughout the follow-up. In the cross-sectional study, AAb+ patients showed a higher percentage of CD14+CD16+ monocytes compared with those with AAb- and the healthy controls (6.70±4.19% versus 4.0±1.84% and 3.44±0.93%; p = 0.026 and 0.009 respectively). Also, CD14+CD16+ monocytes correlated with Hb1Ac and C-pep serum levels. Multivariate logistic regression showed that posttransplant AAb+ was independently associated with a higher percentage of pro-inflammatory monocytes (adjusted-OR 1.59, 95%CI 1.05–2.40, p = 0.027). The group of patients with positive AAb also showed higher levels of IL17A as compared with the other groups (either healthy control or the negative AAb subjects). In conclusion, pancreatic AAb+ after SPK were not only associated with higher Hb1Ac and lower c-peptide serum levels but also with an increased percentage of CD14+CD16+ monocytes and higher levels of circulating IL17-A.

Inhibiting Sphingosine Kinase 2 Derived-sphingosine-1-phosphate Ameliorates Psoriasis-like Skin Disease via Blocking Th17 Differentiation of Naïve CD4 T Lymphocytes in Mice.

Sphingosine-1-phosphate (S1P) is a signalling sphingolipid metabolite that regulates important cell processes, including cell proliferation and apoptosis. Circulating S1P levels have been reported to be increased in patients with psoriasis relative to healthy patients. The aim of this study was to examine the potency of S1P inhibition using an imiquimod-induced psoriasis mouse model. Both topical ceramidase and sphingosine kinase 1/2 inhibition, which blocks S1P generation, alleviated imiquimod-induced skin lesions and reduced the serum interleukin 17-A levels induced by application of imiquimod. These treatments also normalized skin mRNA levels of genes associated with inflammation and keratinocyte differentiation. Inhibition of sphingosine kinase 2, but not sphingosine kinase 1, diminished levels of suppressor of cytokine signalling 1 and blocked T helper type 17 differentiation of naïve CD4+ T cells; imiquimod-induced psoriasis-like skin symptoms were also ameliorated. These results indicate the distinct effects of sphingosine kinase 1 and sphingosine kinase 2 inhibition on T helper type 17 generation and suggest molecules that inhibit S1P formation, including ceramidase and sphingosine kinase 2 inhibitors, as novel therapeutic candidates for psoriasis.

IL-17A contributes to perioperative neurocognitive disorders through blood-brain barrier disruption in aged mice

BackgroundPerioperative neurocognitive disorders (PND) occur frequently after surgery, especially in aged patients. Surgery-induced neuroinflammation and blood-brain barrier (BBB) dysfunction play a crucial role in the pathogenesis of PND. Interleukin-17A (IL-17A) increases after surgical stress and will be involved in BBB dysfunction. However, the effect of IL-17A on BBB function during PND remains poorly understood.MethodsMale wild-type C57BL/6J mice (15 months old) received tibial fracture surgery and fixation to establish the PND model. All the mice were injected intraperitoneally with an IL-17A-neutralizing antibody (Abs) or isotype-control Abs 30 min before tibial fracture surgery. Animal behaviour tests conducted 24 h after surgery included the contextual fear conditioning and Y maze tests. Serum and hippocampus IL-17A levels and hippocampus IL-6 and IL-1β levels were detected by ELISA. BBB function was detected by Evans blue (EB) test. Hippocampus matrix metalloproteinase-2 (MMP-2)- and MMP-9-positive cells were detected by immunohistochemistry. Hippocampus albumin, occludin, claudin-5 and IL-17A receptors were detected by Western blot. For the in vitro experiment, bEnd.3 cells were incubated with IL-17A. Cell IL-17A receptors were detected by immunofluorescence. Cellular MMP-2, MMP-9, occludin, and claudin-5 were detected by Western blot.ResultsTibial fracture surgery promoted memory impairment, increased levels of IL-17A and IL-17A receptors, inflammatory factor production and BBB dysfunction. IL-17A Abs inhibited this effect, including improving memory function, decreasing inflammatory factor production and alleviating BBB disruption, indicated by decreased tight junctions (TJs) and increased MMPs after surgery. The in vitro study suggested that recombinant IL-17A could upregulate the expression of IL-17A receptors, decrease TJs and increase the level of MMPs in bEnd.3 cells.ConclusionsOur results suggested that IL-17A-promoted BBB disruption might play an important role in the pathogenesis of PND.

Correlation of liver function with intestinal flora, vitamin deficiency and IL-17A in patients with liver cirrhosis.

The aim of this study was to investigate the correlation of liver function, intestinal flora, vitamin D and interleukin-17A (IL-17A) levels in patients with liver cirrhosis. A total of 52 patients diagnosed with posthepatitic cirrhosis and admitted into Yantai Infectious Disease Hospital (Yantai, China) from January to December in 2012 (liver cirrhosis group), and 52 patients with chronic hepatitis B (hepatitis group), and 40 healthy volunteers receiving physical examination in the hospital (normal control group) were selected into the study. The liver function, hepatitis B virus (HBV) deoxyribonucleic acid (DNA) level, intestinal flora distribution, vitamin D and IL-17A levels of all patients were detected, and the correlation among them was analyzed via Pearson's analysis. The number of Enterobacteriaceae, Enterococcus, Staphylococcus aureus and Saccharomyces in hepatitis and liver cirrhosis groups was significantly greater than in the normal control group (P<0.05), but the number of Lactobacillus, Bacteroides, Bifidobacterium and Clostridium was significantly decreased (P<0.05); the serum IL-17A levels in hepatitis and liver cirrhosis were obviously higher than that in the normal control group (P<0.05), but the serum vitamin D 25(OH) D and 1,25(OH)2D levels were obviously lower than that in the normal control group (P<0.05). In patients with liver cirrhosis, Enterobacteriaceae was positively correlated with prothrombin time (PT), Enterococcus was positively correlated with alanine aminotransferase and aspartate aminotransferase (AST) levels, Bifidobacterium was negatively correlated with AST, alkline phosphatase (AKP) and HBV DNA levels, and Bacteroides was negatively correlated with AST level and PT. There was a significant negative correlation between serum IL-17A and total bilirubin in patients with liver cirrhosis, and 25(OH) D was negatively correlated with AST, AKP and HBV DNA levels. In patients with liver cirrhosis, there was significant positive correlation between Enterococcus and IL-17A, and between Lactobacillus and 25(OH)D, but other bacteria were not obviously associated with IL-17A and vitamin D. Intestinal flora imbalance, vitamin D deficiency and IL-17A imbalance play an important role in the evolution of liver cirrhosis.