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

Sachiko Matsuzaki, Jean-Luc Pouly, Jean‐Luc Pouly, Michel Canis
Scientific reports · 2020 · vol. 10(1) , pp. 9467 · doi:10.1038/s41598-020-66298-x · PMID:32528066 · PMC7289797 · W3034523650
article OA: gold CC0 ⤵ 11 in-corpus citations
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Low doses of IL-1β and TNFα promote fibrosis in endometriotic stromal cells, while high doses suppress it, unlike in normal endometrial stromal cells.

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

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Condition tags

endometriosis

MeSH descriptors

Endometrium Fibrosis Interleukin-1beta Stromal Cells Tumor Necrosis Factor-alpha Adult Cells, Cultured Endometriosis Endometriosis Endometrium Female Fibrosis Humans Interleukin-1beta RNA, Messenger RNA, Messenger Stromal Cells Tumor Necrosis Factor-alpha Young Adult

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