Interleukin-1 inhibits interleukin-15 production by progesterone during in vitro decidualization in human

Interleukin (IL)-15 is a novel cytokine that plays important roles in uterine natural killer cell function and one of the candidate genes that is upregulated during the window of implantation for human endometrium. IL-15 expression and production by human endometrial stromal cells (ESCs) is elevated during in vitro decidualization by progesterone (P). In the present study, we evaluated the effects of IL-1beta, a proinflammatory cytokine, on IL-15 production in ESCs. By enzyme-linked immunosorbent assay (ELISA), IL-1beta had no effect on IL-15 production from ESCs in short-term culture (for 24 h), whereas IL-1beta stimulated production of IL-8. However, using ELISA and Northern blot analyses we found that IL-1beta significantly inhibited P-induced IL-15 production and mRNA expression in long-term culture (for 12 days) of ESCs in vitro (P<0.01). This inhibition was not due to IL-1beta-mediated cytotoxicity, as ESCs cultured in the presence of IL-1beta showed no evidence of significant change in their viability. These results suggest that ovarian steroid hormones and IL-1beta regulate IL-15 mRNA expression and protein production in long-term culture, and that IL-1beta plays a role as a negative regulator of IL-15 production during decidualization in human endometrium.