Role of interleukin-32 in the pathogenesis of endometriosis: in vitro, human and transgenic mouse data

• Published in: Human reproduction (Oxford) 2018-05, Vol.33 (5), p.807-816
• Main Authors: Lee, Mi-Young, Kim, Sung Hoon, Oh, Young Sang, Heo, Seung-Ho, Kim, Kang-Hyun, Chae, Hee Dong, Kim, Chung-Hoon, Kang, Byung Moon
• Format: Article
• Language: English
• Subjects: Adult; Animals; Ascitic Fluid - metabolism; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Endometriosis - metabolism; Endometrium - metabolism; Female; Humans; Inflammation - metabolism; Interleukins - metabolism; Interleukins - pharmacology; Mice; Mice, Transgenic; Stromal Cells - metabolism
• ISSN: 0268-1161; 1460-2350
• DOI: 10.1093/humrep/dey055

Abstract STUDY QUESTION Does interleukin-32 (IL-32) play a role in the pathogenesis of endometriosis? SUMMARY ANSWER IL-32 might be involved in the pathogenesis of endometriosis through increased viability, proliferation and invasion of endometrial cells. WHAT IS KNOWN ALREADY Endometriosis is characterized as a chronic inflammatory disease and several proinflammatory cytokines are suggested to be involved in its pathogenesis and pathophysiology. IL-32, recognized as a new proinflammatory cytokine and a strong inducer of other proinflammatory cytokines, has been shown to serve as a key modulator in several chronic inflammatory diseases. STUDY DESIGN, SIZE, DURATION This study included comparison of IL-32 levels in the peritoneal fluids between women with and without endometriosis, in-vitro experiments using Ishikawa cells and endometrial stromal cells (ESCs), and experiments on IL-32 transgenic mice and wild-type mice with induced endometriosis. PARTICIPANTS/MATERIALS, SETTING, METHODS IL-32 levels in the peritoneal fluids were measured using enzyme-linked immunosorbent assays. Cell viability, expression of proliferating cell nuclear antigen (PCNA), and cellular invasiveness were analyzed following in-vitro treatment of Ishikawa cells and ESCs with recombinant IL-32 alpha (α) and gamma (γ). Ectopic endometriotic lesions were compared between IL-32 transgenic mice and wild-type mice after autologous endometrial transplantation with immunohistochemistry for Ki-67 antigen and PCNA. MAIN RESULTS AND THE ROLE OF CHANCE The peritoneal fluid concentration of IL-32 was significantly higher in patients with advanced stage endometriosis compared with the controls. In-vitro treatment with IL-32 α and γ caused significant increases in cellular viability, PCNA expression, and invasiveness in Ishikawa cells and ESCs. The IL-32 transgenic mice had a significantly larger size of the ectopic endometrial lesions with higher expression of Ki-67 antigen and PCNA compared with wild-type mice. LARGE SCALE DATA N/A LIMITATIONS, REASONS FOR CAUTION It is still unclear whether IL-32 is a main regulator, or one of several downstream proinflammatory cytokines, causing establishment and/or progression of endometriosis. WIDER IMPLICATIONS OF THE FINDINGS Further investigation on IL-32 signaling pathways may contribute to development a more effective treatment of endometriosis. STUDY FUNDING/COMPETING INTEREST(S) This research was supported by a grant of the Korea Health Technology R&D