Interleukin-17

Introduction: Depression is a mental disorder that highly associated with immune system.
Therefore, this study compares the serum concentrations of IL-21, IL-17, and transforming
growth factor β (TGF-β) between patients with major depressive disorder and healthy controls.
Methods: Blood samples were collected from 41 patients with major depressive disorder and
40 healthy age-matched controls with no history of malignancies or autoimmune disorders. The
subjects were interviewed face to face according to DSM-IV diagnostic criteria. Depression
score was measured using completed Beck Depression Inventory in both groups. The serum
concentrations of IL-21, IL-17, and TGF-β were assessed using ELISA.
Results: The mean score of Beck Depression score in the patient and control groups was
35.4±5.5 and 11.1±2.3. IL-17 serum concentrations in the patients and the control group were
10.03±0.6 and 7.6±0.6 pg/mL, respectively (P=0.0002). TGF-β level in the patients group was
significantly higher than compare to the control group; 336.7±20.19 vs. 174.8±27.20 pg/mL,
(P<0.0001). However, the level of IL-21 was not statistically different between the two groups
84.30±4.57 vs. 84.12±4.15 pg/mL (P>0.05).
Conclusion: Considering pro-inflammatory cytokines, current results support the association
of inflammatory response and depressive disorder. So, it seems that pro-inflammatory factors
profile can be used as indicator in following of depression progress and its treatment impacts.

Background: The number of patients with Multiple Sclerosis (MS) is increasing in Iran. Studies have shown that high sodium chloride (salt) and low potassium intake are associated with the development of MS. High physiological salt concentrations can lead to the induction of Interleukin-17 (IL-17) accompanied by the excessive generation of helper T-17 cells (Th-17). This cytokine plays a critical role in the pathogenesis of autoimmune diseases. This is while potassium supplementation has a blocking effect on IL-17 production. Objectives: Because of the role of salt and potassium in Th 17 development, we hypothesized that sodium chloride (NaCl) would be higher and potassium (K) would be lower in MS patients than healthy controls. Therefore, we investigated the association between salt and potassium intake with MS in Isfahan City population, Iran. Materials and Methods: A case-control study containing 23 patients and 23 healthy controls was performed in Isfahan City, Iran, 2016. NaCl and K levels were measured in 24-h urine. Using the Chi-square test, the patients' laboratory values were compared with the healthy controls. The level of significance was set at P<0.05 in all analyses. All calculations were performed in SPSS, version 23.0. Results: In this study, urine Na levels were somewhat higher in cases than in controls (Interquartile Range [IQR]; 160[140-211] mEq/24 h vs. 128[83-166] mEq/24 h]) (P=0.027). These results show a significant relationship between urine-Na and MS. Urine k concentrations were lower in cases than controls [IQR; 47(27-70) mEq/24 h vs. 50(29-56) mEq/24 h] but we did not find a significant difference between two groups (P=0.807). Conclusion: Based on this study, a high level of sodium intake may be associated with MS; however, we did not find a significant difference between patients and controls with regard to potassium level.

"Interleukin-17 (IL-17) has emerged as a central player in the mammalian immune system. Although this cytokine exerts a host-defensive role in many infectious diseases, it promotes inflammatory pathology in autoimmunity and other settings. A myriad of studies have focused on how IL-17-producing cells are generated. However, the means by which IL-17 achieves its effects, either for the benefit or the detriment of the host, are due in large part to the induction of new gene expression. Whereas many IL-17 target genes are common to different disease states, in some cases the effects of IL-17 differ depending on the target cell, infectious site or pathogen. Gene products induced by IL-17 include cytokines (IL-6, granulocyte-colony-stimulating factor, tumour necrosis factor-a), chemokines (CXCL1, CXCL2, CCL20, among many others), inflammatory effectors (acute-phase protesins, complement) and antimicrobial proteins (defensins, mucins). Different cell types appear to respond differently to IL-17 in terms of target gene expression, with notable differences seen in mesenchymal and epithelial cells compared with cells of haematopoietic origin. Here, we summarize the major IL-17 target genes that mediate this cytokine’s activities in both autoimmune and chronic diseases as well as during various types of infections."

Conclusion: The variant IL-17A-197A allele and IL-17F 7488CC genotype were associated with increased risk of cancer, especially for gastric cancer.

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Regardless of abundant efforts to enhance primary prevention and early detection, the number of melanoma cases in the United States has increased steadily over the past 15 years, thus greatly affecting public health and the economy. In previous studies, we demonstrated protein kinase C-ι (PKC-ι) to be an oncogene in melanoma, which promotes the activation of nuclear factor (NF)-κB, thereby supporting survival and progression. In addition, we demonstrated that PKC-ι induced the metastasis of melanoma cells by activating Vimentin, and PKC-ι inhibition downregulated epithilial-mesencymal transition (EMT), while inducing apoptosis. Of note, PKC-ι specific inhibitors downregulated the expression of both PKC-ι and phosphorylated PKC-ι, suggesting that PKC-ι plays a role in regulating its own expression in melanoma. In this study, we report the underlaying mechanisms of the transcriptional regulation of PKC-ι (PRKCI gene) expression in melanoma. c-Jun, interferon-stimulated gene factor 3 (ISGF3), paired box gene 3 (PAX3), early growth response protein 1 (EGR1) and Forkhead box protein O1 (FOXO1), which bind on or near the promoter sequence of the PRKCI gene, were analyzed for their role in PKC-ι regulation in SK-MEL-2 and MeWo cell lines. We silenced selected transcription factors using siRNA, and the results revealed that the silencing of c-Jun and FOXO1 significantly altered the expression of PRKCI. The levels of both phosphorylated and total PKC-ι increased upon FOXO1 silencing and decreased upon c-Jun silencing, suggesting that c-Jun acts as an upregulator, while FOXO1 acts as a down-regulator of PRKCI expression. We also used a multiplex ELISA to analyze multiple pathways other than NF-κB that were affected by treatment with PKC-ι inhibitor. The silencing of NF-κB p65 and PKC-ι by siRNA suggested that the regulation of PKC-ι expression was strongly associated with FOXO1. In addition, we observed a significant decrease in the mRNA levels of both interleukin (IL)-6 and IL-8, with a significant increase in the levels of IL-17E and intercellular adhesion molecule 1 (ICAM-1) upon the knockdown of expression of PKC-ι in both cell lines. This suggested that PKC-ι expression was affected by these cytokines in an autocrine manner. Overall, the findings of this study suggest that PKC-ι inhibition suppresses its own expression, diminishing oncogenic signaling, while upregulating anti-tumor signaling, thus rendering it an effective novel biomarker for use in the design of novel targeted therapeutics for melanoma.

Type 1 diabetes mellitus (T1D) is a T cell-mediated autoimmune disease that cause destruction of
pancreatic islet β- cells. Susceptibility to T1D is determined by interaction between several genetic loci and
environmental factors. Alleles at the human leukocyte antigen (HLA) locus explain up to 50% of the
familial clustering of T1D, but other loci are also contributed to T1D and there is a universal trial to
understand their role in this complex disease. In addition, there is a consensus among epidemiologists that
the worldwide incidence rate of type 1 diabetes has been rising in recent decades. The cause of this rise is
unknown, but epidemiological studies suggest the involvement of environmental factors, and viral
infections in particular.
Finding new loci and the pathways in which the destruction of β-cells happen, can lead to possible
diagnostic and therapeutic applications of these genetic findings. Also, determining the environmental
factors causing T1D is useful, because we can eliminate them and trying to prevent the disease in
susceptible individuals by this knowledge.