Role of cytokines in development of endometriosis

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We have measured peritoneal fluid (PF) levels of matrix metalloproteinase-9 (MMP-9), its inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1) and interleukin-10 (IL-10) in patients with endometriosis. Although the concentrations of MMP-9 was below the detectable level, high concentrations of TIMP-1 and IL-10 were present in the PF. The levels of IL-10 in PF was significantly higher in patients with endometriosis than in patients without endometriosis. In order to examine the effects of IL-6 or IL-10 on the gene expression of TIMP-1, endometrial and endometriotic stromal cells were collected from the uterus or from ovarian chocolate cysts. The stimulatory effects of these cytokines have been elucidated.We have conducted the study to investigate the possible role of IL-6, soluble IL-6 receptor in the growth of endometrial and endometriotic cells. We examined the effect of IL-6, soluble IL-6 receptor or combination of both factors on the proliferation of endometrial and endometriot … More ic stromal cells. IL-6 receptor had no effect on the growth of stromal cells in tissue from the proliferative phase. In contrast, the addition of 200 or 400pg/ml of IL-6 induced significant inhibition of cell proliferation. Similarly, the addition of soluble IL-6 receptor caused significant suppression in the growth of endometrial stromal cells in tissue from the secretory phase, but not the proliferative phase. On the other hand, stromal cells of endometriotic tissues were resistant to IL-6, showing no inhibitory response. Although the combination treatment did not affect the proliferation of stromal cells of proliferative phase and of endometriotic tissues, 10gn/ml of soluble IL-6 inhibited proliferation of stromal cells of the secretory phase in the presence of 1ng/ml of soluble IL-6 receptor. The expression of transcripts of IL-6 receptor and gp130 was observed in the endometrial cells from the proliferative and secretory phases and in endometriotic cells. IL-6 may play a central role in regulation of the growth of endometrial cells as a mediator of endocrine action. Endometriotic cells may behave differently from the normal counterpart in terms of the inhibitory regulation exerted by IL-6. Less