Interleukin‐9 produced by helper T cells stimulates interleukin‐8 expression in endometriosis
Yosuke Tarumi, Taisuke Mori, Hiroyuki Okimura, Eiko Maeda, Yukiko Tanaka, Hisashi Kataoka, Fumitake Ito, Akemi Koshiba, Izumi Kusuki, Jo Kitawaki
Abstract
PROBLEM: Inflammation and immune responses play crucial roles in the development of endometriosis. Although interleukin-9 (IL-9) has a pro-inflammatory function in chronic inflammatory diseases, its function in endometriosis remains unknown. Here, we aimed to investigate the significance of IL-9 and IL-9-producing lymphocytes in endometriosis. METHOD OF STUDY: lymphocytes and IL-9 concentration using flow cytometry and enzyme-linked immunosorbent assay. OE, endometrium with endometriosis (EE), and normal endometrium (NE) were analyzed for IL-9 receptor (IL-9R) expression using immunohistochemical staining. IL-9-dependent changes in Interleukin-8 (IL-8) expression in endometrial stromal cells from OE (OESCs) were evaluated using real-time PCR. RESULTS: lymphocytes was higher in the PF, but not the PB, of patients with endometriosis than individuals without endometriosis (p < .05). However, IL-9 levels in the PF did not differ between those with and without endometriosis. We detected CD4+ IL-9+ lymphocytes in OE tissues and IL-9R in OE tissues and OESCs. In OESC culture, IL-9 significantly elevated IL-8 expression in a dose-dependent manner (p < .05), which was nullified by the addition of the anti-IL-9 receptor antibody. Furthermore, IL-9 additively stimulated IL-8 expression in the presence of TNF-α (p < .05). CONCLUSION: Our findings show that IL-9 produced by helper T cells induces IL-8 expression, suggesting that IL-9 plays an important role in the development of endometriosis by stimulating IL-8 expression.