Interleukin-17

"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."

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.

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.

Psoriasis is a chronic, relapsing, immune-mediated systemic disease. Its pathogenesis is complex and not fully understood yet. Genetic and epigenetic factors interact with molecular pathways involving TNF-α, IL-23/IL-17 axis, and peculiar cytokines, as IL-36 or phosphodiesterase 4. This review discusses the mechanisms involved in the development of the disease, as well as the therapeutic options proposed following the investigation of the inflammatory psoriatic pathways. We performed a comprehensive search using the words "psoriasis" and the newest molecules currently under investigation and approval. From these data, a new scenario in psoriasis is occurring to personalize the therapies-especially systemic ones and those using small molecules-and avoid topical and injectable drugs. We reported the newest therapeutic opportunities, including the inhibitors of Janus kinase/ tyrosine kinase 2, phosphodiesterase-4 and IL-36 receptor. Today, more than 20 molecules are under investigation for the treatment of cutaneous psoriasis. Most of them are constituted by small molecules or biologic therapies. This underlines how psoriasis needs systemic therapies, due to its complex pathogenesis and multisystemic involvement.

Objective The Pathological symptoms of Alzheimer’s disease and the degeneration of nerve cells cause
inflammation in these patients. This study aimed to investigate the effect of endurance training and saffron
extract on the plasma levels of interleukin 17 and 18 in Alzheimer’s rats by trimethyltin chloride.
Methods This experimental study was conducted on 32 male Sprague-Dawley rats weighing 180±20
grams. After Alzheimer’s induction (by the intraperitoneal injection of 80 mg/kg trimethyltin chloride),
the rats were randomly assigned into four groups: Control, training, saffron extract, saffron extract + training.
The saffron extract was injected intraperitoneally at the dose of 25 mg/kg, daily, for eight weeks. Also,
the endurance training program consisted of incremental running on the treadmill at a speed of 15 to
20 m/min. The program was performed in 15 to 30 minutes sessions, three sessions per week, for eight
weeks. Finally, the obtained data were analyzed using two-way ANOVA at the P<0.05.
Results The results showed that exercise (P=0.10), saffron consumption (P=0.07), and the interaction of
exercise and saffron consumption (P=0.06) did not significantly affect interleukin 17, in rats. Also, exercise
(P=0.68), saffron consumption (P=0.84), and the interaction of exercise and saffron consumption (P=0.57)
had no significant effect on interleukin 18, in rats.
Conclusion According to the results, it seems that exercise training and saffron extract do not affect the
interleukin 17 and interleukin 18 in Alzheimer’s rats.