A comprehensive network map of IL-17A signaling pathway

Abstract

Interleukin-17A (IL-17A) is one of the member of IL-17 family consisting of other five members (IL-17B to IL-17F). The Gamma delta (γδ) T cells and T helper 17 (Th17) cells are the major producers of IL-17A. Aberrant signaling by IL-17A has been implicated in the pathogenesis of several autoimmune diseases including idiopathic pulmonary fibrosis, acute lung injury, chronic airway diseases, and cancer. Activation of the IL-17A/IL-17 receptor A (IL-17RA) system regulates phosphoinositide 3-kinase/AKT serine/threonine kinase/mammalian target of rapamycin (PI3K/AKT/mTOR), mitogen-activated protein kinases (MAPKs) and activation of nuclear factor-κB (NF-κB) mediated signaling pathways. The IL-17RA activation orchestrates multiple downstream signaling cascades resulting in the release of pro-inflammatory cytokines such as interleukins (IL)-1β, IL-6, and IL-8, chemokines (C-X-C motif) and promotes neutrophil-mediated immune response. Considering the biomedical importance of IL-17A, we developed a pathway resource of signaling events mediated by IL-17A/IL-17RA in this study. The curation of literature data pertaining to the IL-17A system was performed manually by the NetPath criteria. Using data mined from the published literature, we describe an integrated pathway reaction map of IL-17A/IL-17RA consisting of 114 proteins and 68 reactions. That includes detailed information on IL-17A/IL-17RA mediated signaling events of 9 activation/inhibition events, 17 catalysis events, 3 molecular association events, 68 gene regulation events, 109 protein expression events, and 6 protein translocation events. The IL-17A signaling pathway map data is made freely accessible through the WikiPathways Database (https:// www. wikip athwa ys. org/ index. php/ Pathw ay: WP5242).

RETRACTED ARTICLE: Qilongtian ameliorate bleomycin-induced pulmonary fibrosis in mice via inhibiting IL-17 signal pathway

“…Aberrant signaling of IL-17 implicates the pathogenesis of several autoimmune diseases, including idiopathic pulmonary fibrosis, acute lung injury, chronic airway disease, and cancer 58 . Literature research on the enrichment gene of the IL-17 signaling pathway in the first place showed that CCL12 chemokine produced by macrophages and epithelial cells is a fibrogenic medium, and CCL12 could promote the development of fibrosis [59][60][61] . Pena-Philippides et al 62 reported that CCL12 and CXCL5 cytokine expression affect the secretion of IL-17.…”

Serum beta‐defensin‐2 is a biomarker for psoriasis but not subclinical atherosclerosis: Role of IL17a, PI‐3 kinase and Rac1

“…After 1 year, all three groups had an improvement in psoriasis severity which was significant (anti-TNF-α; 8.9 (6.0-14.7) to 2.7 Next, we tested whether changes in serum BD2 were concomitant with a reduction of psoriasis severity (Table 2). We found that patients undergoing anti-TNFα biologic treatment over 1 year exhibited a 51% reduction in serum BD2 (27,499.3 ng/mL, p = 0.0062) and those treated with anti-IL17A, a 45.8% reduction (72,866.9-39,503 ng/mL, p = 0.0046). However, a significant reduction (12.9%) in serum BD2 was not observed in patients lacking biological therapy (87,281.1-76,068.66 ng/mL, p = 0.127), though psoriasis disease severity was diminished (p = 0.0249).…”

Synergistic effects of COVID-19 and Pseudomonas aeruginosa in chronic obstructive pulmonary disease: a polymicrobial perspective

“…Altered bursts of IL-6 in COPD have been reported, which may make the system more susceptible to SARS-CoV-2 in-burst. Upregulated concentrations of Th2/M2 cytokines, including IL-6, CCL22, IL-4, IL-13, and IL-10, were observed in the bronchoalveolar lavage of COPD individuals, with IL-13 being particularly elevated [ 26 , 27 ].…”