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

ABSTRACT: 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? (IL-1?) and tumor necrosis factor-alpha (TNF?) promoted a fibrotic phenotype, whereas high levels of IL-1? and TNF? inactivated the fibrotic phenotype of endometriotic stromal cells (Ectopic-ES). IL-1? 10?pg/mL and TNF? 100 and 1,000?pg/mL had minimal effects, whereas the highest dose of IL-1? (100?pg/mL) significantly decreased collagen gel contraction in Ectopic-ES. Furthermore, in Ectopic-ES, low levels of IL-1? (1?pg/mL) and/or TNF? 10?pg/mL significantly increased Col I mRNA expression, whereas higher doses of IL-1? (10 and/or 100?pg/mL) and/or TNF? (100 and/or 1,000?pg/mL) significantly decreased Col I and/or ?SMA mRNA expression and the percentage of cells with Col I?+?and/or ?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? and/or TNF? had no significant effects on either Col I or ?SMA mRNA/protein expression. The present findings bring into question whether we should still continue to attempt anti-inflammatory treatment strategies for endometriosis.

SUBMITTER: Matsuzaki S 

PROVIDER: S-EPMC7289797 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature