Interleukin 1 regulates its own receptors in human endometrial cells via distinct mechanisms

Interleukin 1 (IL1) plays an important role in the physiology of human endometrium and is recognized as a major and early embryonic signal. Tight control over the local endometrial action of this cytokine is critical for normal reproductive functions. The coordinated regulation of IL1 receptors types I and II (IL1R1 and IL1R2) and IL1 receptor antagonist (IL1RA) in endometrial cells may represent one of the principle mechanisms involved in the control of IL1 local effects. The objective of this study was to investigate the regulation of IL1Rs in human endometrial epithelial cells in response to IL1. Cultures of KLE endometrial epithelial cell line and primary human endometrial epithelial cells, immunofluorescent staining, enzyme-linked immunosorbent assay, western blotting, nuclear transcription (run-on) and real-time PCR were used to investigate the expression of IL1R1, IL1R2 and IL1RA. Cells appeared to react to IL1 by up-regulating the expression of the signaling activating IL1R1 and to moderate in parallel IL1 effects by elevating the expression of the decoy inhibitory IL1R2 and the receptor antagonist IL1RA. Regulation of IL1R1 and IL1RA by IL1B involved gene transcription activation and that of IL1R2 involved mRNA stabilization. Considering IL1's immunomodulatory, proangiogenic and tissue remodeling properties, and its role as an embryonic signal, modulation of endometrial cell responsiveness to IL1 via the concomitant regulation of its own activating and inhibitory receptors and receptor antagonist may represent an important regulatory mechanism of IL1-induced physiological changes occurring in the human endometrium during the normal menstrual cycle and embryo development.