Disease relevance of IL17A

• Association analysis of the interleukin 17 genes IL17A and IL17F as potential osteoarthritis susceptibility loci [1].
• Analysis of the cDNA encoding murine interleukin (IL) 17 (cytotoxic T lymphocyte associated antigen 8) predicted a secreted protein sharing 57% amino acid identity with the protein predicted from ORF13, an open reading frame of Herpesvirus saimiri [2].
• Role of IL-17A, IL-17F, and the IL-17 receptor in regulating growth-related oncogene-alpha and granulocyte colony-stimulating factor in bronchial epithelium: implications for airway inflammation in cystic fibrosis [3].
• IL-17 expression in human herpetic stromal keratitis: modulatory effects on chemokine production by corneal fibroblasts [4].
• CONCLUSIONS: Gingival concentrations of IL-11 and IL-17 are different in diseased gingiva adjacent to 3, 4 to 5, and > or = 6 mm pockets, suggesting that their concentrations change as a consequence of the progression of gingivitis to periodontitis and that both cytokines could have a significant role in this progression [5].
• IL-17 family members are varyingly expressed in rheumatoid nodules [6].

Psychiatry related information on IL17A

• Analyses by ELISA showed that IL-17 protein was undetectable in 48.6% of the patients with cancer, as well as corresponding normal tissue which may in part reflect an individual difference [7].

High impact information on IL17A

• IL-17 Family Cytokines and the Expanding Diversity of Effector T Cell Lineages [8].
• Because of its importance for Treg cells, we examined the role of IL-2 in Th17 generation and demonstrate that a previously unrecognized aspect of IL-2 function is to constrain IL-17 production [9].
• Intestinal inflammation was associated with IL-23 (p19) mRNA-producing intestinal dendritic cells and IL-17A mRNA within the intestine [10].
• Increasing evidence shows that IL-17 family members play an active role in inflammatory diseases, autoimmune diseases, and cancer [11].
• IL-17A is largely produced by activated memory T lymphocytes but stimulates innate immunity and host defense [11].

Chemical compound and disease context of IL17A

• Interestingly, synovial fluid cells, in contrast to PBMCs isolated from patients with rheumatoid arthritis, but not osteoarthritis, respond to PMA + ionomycin with much lower, comparable to IL-15-triggered IL-17 secretion [12].
• In the CSF supernatant, a significant increase of IL-17, IL-8 and IL-6, and a significant decrease of IL-4, IL-5 and IL-7 levels were detected in pretreated CIDP as compared with OND [13].
• IL-11 and IL-17 expression in nasal polyps: relationship to collagen deposition and suppression by intranasal fluticasone propionate [14].
• Murine Meth-A fibrosarcoma cells were transfected with the hIL-17 gene using the lipofectin method [15].

Biological context of IL17A

• These observations suggest that hIL-17 may constitute (a) an early initiator of the T cell-dependent inflammmatory reaction; and (b) an element of the cytokine network that bridges the immune system to hematopoiesis [2].
• Furthermore, transfection studies using a luciferase-driven reporter construct containing eotaxin-1/CCL11 proximal promoter showed that IL-17A induced eotaxin-1/CCL11 at the transcriptional level [16].
• RESULTS: Compared with IFN-gamma, CM of either cell type stimulated with IL-1beta, or in the case of HCE cells, stimulated with TNF-alpha or IL-17, delayed neutrophil apoptosis significantly [17].
• Further, IL-17 induced the phosphorylation of src kinase and mitogen-activated protein (MAP) kinase [18].
• Collectively, we have identified IL-22 as a new cytokine expressed by Th17 cells that synergizes with IL-17A or IL-17F to regulate genes associated with skin innate immunity [19].

Anatomical context of IL17A

• Furthermore, when cultured in the presence of hIL-17, fibroblasts could sustain the proliferation of CD34+ hematopoietic progenitors and their preferential maturation into neutrophils [2].
• IL-17 is a recently discovered cytokine that can be released from activated human CD4+ T lymphocytes [20].
• These data demonstrate that hIL-17 can specifically and selectively recruit neutrophils into the airways via the release of C-X-C chemokines from bronchial epithelial cells and suggest a novel mechanism linking the activation of T-lymphocytes to recruitment of neutrophils into the airways [20].
• Here we show that IL-17 is expressed in corneas from patients with HSK and that the IL-17R is constitutively expressed by human corneal fibroblasts (HCF) [4].
• In this study, we investigated the molecular mechanisms involved in IL-17A-mediated CC chemokine (eotaxin-1/CCL11) production from human airway smooth muscle (ASM) cells [16].

Associations of IL17A with chemical compounds

• Moreover, IL-17A significantly induced eotaxin-1/CCL11 release and mRNA expression, an effect that was abrogated with cycloheximide and actinomycin D treatment [16].
• Adding IL-17 increased prostaglandin E2 (PGE2) synthesis in cocultures of bone marrow cells and osteoblasts and in single cultures of osteoblasts, but not in single cultures of bone marrow cells [21].
• Direct interaction between osteoclast progenitors and osteoblasts was required for IL-17-induced osteoclastogenesis, which was completely inhibited by adding indomethacin or NS398, a selective inhibitor of cyclooxgenase-2 (COX-2) [21].
• Unexpectedly, the crystal structure of IL-17F reveals that IL-17 family members adopt a monomer fold typical of cystine knot growth factors, despite lacking the disulfide responsible for defining the canonical "knot" structure [22].
• Importantly, dexamethasone blunted IL-17-dependent activation of MAP kinases, suggesting a mechanistic relationship between these activities and the aforementioned gene expression responses [23].

Physical interactions of IL17A

• Binding studies suggest that recombinant hIL-17 binds to the hIL-17R with low affinity [24].

Regulatory relationships of IL17A

• This effect of hIL-17 was inhibited by cotreatment with an anti-hIL-17 Ab and was potentiated by hTNF-alpha [20].
• IL-6 secretion was rapidly induced by IL-17, IL-1beta, and TNF-alpha [25].
• We conclude that CO inhibits IL-17-stimulated inflammatory response via the ERK1/2-dependent pathway [26].
• Pharmacological drugs used in therapy of RA, such as cyclosporin and methotrexate, induced a fourfold increase of IL-17R mRNA expression and augmented the IL-17-stimulated IL-8 expression [27].
• In this study, we investigated the effects of IL-17 on colony-stimulating factor (CSF) release in human colonic subepithelial myofibroblasts (SEMFs) [28].
• CCR6 was likewise expressed on all IL-17-producing CD8+ PBL [29].

Other interactions of IL17A

• The effect of hIL-17 on the release of hIL-8 and rMIP-2 was also inhibited by glucocorticoids, in vitro and in vivo, respectively [20].
• IL-17 exhibited a strong synergistic effect with TNF-alpha on the induction of IL-6 and IL-8 secretion by cultured HCF [4].
• We hypothesized that IL-17, a mediator predominantly released by memory T cells and present in airways of individuals with asthma, would modulate rather than induce IL-8 and IL-6 production by both human lung epithelial cells and fibroblasts [30].
• In this study, we investigated the roles of CD4 T cell cytokines IL-17 and IL-17F in GM-CSF production from lung microvascular endothelial cells (LMVECs) [31].
• In conclusion, it becomes clear that IL-17 is an inducer of IL-8 and MCP-1 secretion by human fetal intestinal epithelial cells [32].

Analytical, diagnostic and therapeutic context of IL17A

• This recruitment of neutrophils into the airways was inhibited by an anti-hIL-17 Ab and accompanied by increased levels of rat macrophage inflammatory protein-2 (rMIP-2) in bronchoalveolar lavage (BAL) fluid [20].
• The carcinoma cell lines DU145, PC3, LNCaP, and BPH-epithelial (EC), stromal cell (SC) preparations, and BPH-T-cell lines were analyzed for IL-17 production by RT-PCR and ELISA [33].
• Immunohistochemistry was used to localize both IL-17 and IL-17 receptor [33].
• In our previous study, we found that IL-17 expressed early on borderline change of renal allograft rejection by Banff classification both in rat renal allograft model and human renal specimens [18].
• Activation of mitogen-activated protein (MAP) kinases in both IL-17-stimulated MKN28 cells and epithelial cells isolated from H. pylori-colonized gastric mucosa was assessed by Western blotting [34].

References