Cycle-dependent expression of interleukin-1 receptor type II in the human endometrium

Cytokines such as interleukin-1 (IL-1) play a major role in the reparative and inflammatory-like processes that occur in human endometrium during ever y menstrual cycle, but they also seem to be implicated in critical reproduc tive events such as ovulation and implantation. Interleukin-1 is tightly re gulated in the body by a complex network of control systems. In the present study, we examined the expression of IL-1RII, a natural specific inhibitor of IL-1, in the human endometrium and found an interesting distribution an d temporal pattern of expression throughout the menstrual cycle. Immunoreac tive IL-1RII was found in stromal as well as epithelial cells, but it was p redominant within the lumen of the glands and the apical side of surface ep ithelium. in situ hybridization and reverse transcription-polymerase chain reaction (RT-PCR) analyses showed higher levels of mRNA in epithelial than in stromal cells. The IL-1 RI I cellular and luminal secretion followed a r egulated cycle phase-dependent pattern of expression. Although elevated in the late proliferative/early secretory phase of the menstrual cycle, IL-1RI I luminal secretion significantly decreased in the midsecretory phase, reac hing its lowest levels at Day 21, before augmenting markedly again during t he late secretory phase. This pattern of expression was less obvious at the level of cellular staining, as examined by immunohistochemistry, but it wa s corroborated by Western blot analysis of IL-1RII protein and semiquantita tive RT-PCR of IL-1RII mRNA in the whole endometrial tissue and separated g landular epithelial cells. The reduced expression of IL-1RII within the imp lantation window suggests the existence of accurate regulatory mechanisms t hat, by down-regulating IL-1RII expression, alleviate IL-1 inhibition durin g this crucial period and facilitate IL-1 proimplantation actions. The elev ated expression of IL-1RII observed during the late secretory phase suggest s an involvement of IL-1RII in control of the proinflammatory state that ta kes place in the endometrium during the premenstrual and menstrual periods.