Luteolin inhibits IL-33/ST2L-induced M2 macrophage polarization in endometriosis

Wei Wang, Y C Chen, Chen Y, Yanran Chen, Wang W, Wenxin Wang, Jiang L, Linhong Jiang, Dandan Bai, Bai D, Yunjun Yang, Yang Y, Y F Yang, Haixia Wang, Wang H, Wang M, Mengyuan Wang, Si H, Haipeng Si, Jun Long, Long J, Yuan D, Dongping Yuan, Li J, Jin Li
Molecular immunology · 2026 · vol. 195 , pp. 172–185 · doi:10.1016/j.molimm.2026.05.008 · PMID:42167049 · W7162109101
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Luteolin inhibits IL-33/ST2L signaling to suppress M2 macrophage polarization, reduce human endometrial stromal cell proliferation and migration, and ameliorate the local immune microenvironment in an endometriosis mouse model.

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Abstract

BACKGROUND: Endometriosis is a chronic inflammatory disease characterized by immune microenvironment dysregulation, with the IL-33/ST2L signaling axis playing a crucial role in macrophage polarization and disease progression. Despite growing evidence of IL-33's involvement in endometriosis pathogenesis, the mechanisms underlying IL-33-induced macrophage polarization and the therapeutic potential of a natural immunomodulator luteolin remain incompletely understood. METHODS: We investigated the effects of luteolin on IL-33/ST2L-mediated M2 macrophage polarization using in vitro cell culture models and an in vivo mouse endometriosis model. The proliferation and migration of human endometrial stromal cells (HESCs) were assessed following macrophage co-culture experiments. The MyD88/NF-κB signaling pathway and inflammatory cytokine expression were analyzed using Western blotting, RT-PCR, and ELISA. RESULTS: IL-33 significantly promoted M2 macrophage polarization, which subsequently enhanced HESC proliferation and migration. Luteolin treatment effectively suppressed IL-33/ST2L signaling, inhibited IL-33-induced M2 macrophage polarization, and reduced HESC proliferative and migratory activities. In the mouse endometriosis model, luteolin administration decreased IL-33 secretion, prevented M2 macrophage accumulation, and downregulated the MyD88/NF-κB pathway. This resulted in significant reduction of pro-inflammatory cytokines (IL-1β, TNF-α, IL-4, and IL-13) and amelioration of the local immune microenvironment. CONCLUSIONS: Our findings demonstrate that luteolin exerts therapeutic effects in endometriosis by disrupting IL-33/ST2L-mediated M2 macrophage polarization and modulating inflammatory responses. These results suggest that luteolin is a promising natural therapeutic candidate for endometriosis treatment, offering insights into immune-targeted therapeutic strategies.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis

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Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

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