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

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 Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant number: HI16C1682). None of the authors has anything to disclose.