Increased expression of interleukin-1 receptor type 1 in active endometriotic lesions

Abstract

The establishment and progression of ectopic endometrial implants are dependent upon their interaction with and responsiveness to the stimuli present in their new environment. According to our and other previous studies, immune cells-derived cytokines, such as IL-1, may alone or in concert with estrogens, enhance the capability of ectopic endometrial cells to implant and develop into the host tissue. In the present study, immunohistochemical and dual immunofluorescence analyses showed that the functional signaling interleukin-1 receptor type 1 (IL-1RI) is expressed in endometriotic tissue, particularly in the glands, and identified endothelial cells, macrophages, and T-lymphocytes as cells having marked expression of IL-1RI. The highest concentrations of IL-1RI protein in endometriotic tissue, as evaluated using histological score (HSCORE) and measured by ELISA, were found in red endometriotic lesions as compared with typical black-blue or white lesions. Western blotting showed a significant increase in the levels of the 50 kDa band, whose apparent molecular weight corresponds to the soluble form of IL-1RI. RT-PCR analysis of IL-1 mRNA levels showed a pattern of expression comparable to that of the protein. Interestingly, IL-1RI expression was more significant in the proliferative than in the secretory phase of the menstrual cycle. Marked expression of IL-1RI, the functional signaling receptor that mediates cell activation by IL-1, in red endometriotic implants, which are highly vascularized and represent the earliest and most active forms of the disease, point to a higher cell receptivity for IL-1 in these lesions, a relationship with the activity of the disease and a possible involvement in the early steps of endometriotic tissue growth and development.