Dose-dependent pro- or anti-fibrotic responses of endometriotic stromal cells to interleukin-1β and tumor necrosis factor α

Endometriosis are characterized by dense fibrous tissue. Numerous studies have investigated roles of inflammation on the pathophysiology of endometriosis. However, the interplay of inflammation and fibrosis remains to be clarified. Here we show that low levels of interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF alpha) promoted a fibrotic phenotype, whereas high levels of IL-1 beta and TNF alpha inactivated the fibrotic phenotype of endometriotic stromal cells (Ectopic-ES). IL-1 beta 10pg/mL and TNF alpha 100 and 1,000pg/mL had minimal effects, whereas the highest dose of IL-1 beta (100pg/mL) significantly decreased collagen gel contraction in Ectopic-ES. Furthermore, in Ectopic-ES, low levels of IL-1 beta (1pg/mL) and/or TNF alpha 10pg/mL significantly increased Col I mRNA expression, whereas higher doses of IL-1 beta (10 and/or 100pg/mL) and/or TNF alpha (100 and/or 1,000pg/mL) significantly decreased Col I and/or alpha SMA mRNA expression and the percentage of cells with Col I+and/or alpha SMA+stress fibers. In contrast, in either menstrual endometrial stromal cells of patients with endometriosis or those of healthy women, varying doses of IL-1 beta and/or TNF alpha had no significant effects on either Col I or alpha SMA mRNA/protein expression. The present findings bring into question whether we should still continue to attempt anti-inflammatory treatment strategies for endometriosis.