Endometriotic inflammatory microenvironment induced by macrophages can be targeted by niclosamide†

Nikola Sekulovski, Allison E Whorton, Mingxin Shi, Shi M, James A. MacLean, Kanako Hayashi
Biology of reproduction · 2018 · vol. 100(2) , pp. 398–408 · doi:10.1093/biolre/ioy222 · PMID:30329025 · PMC6378864 · W2896081714
article OA: bronze CC0 ⤵ 17 in-corpus citations
📄 Open PDF View on OpenAlex View on PubMed View at publisher
⚙ AI-generated summary by gemini-2.5-flash-lite, 2026-06-08 ⓘ

Niclosamide inhibits endometriotic epithelial cell viability and reduces inflammatory cytokine secretion induced by macrophages by targeting STAT3 and/or NF-κB signaling.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

Abstract

Endometriosis causes severe chronic pelvic pain and infertility. We have recently reported that niclosamide treatment reduces growth and progression of endometriosis-like lesions and inflammatory signaling (NF${\rm \small K}$B and STAT3) in a mouse model. In the present study, we examined further inhibitory mechanisms by which niclosamide affects endometriotic lesions using an endometriotic epithelial cell line, 12Z, and macrophages differentiated from a monocytic THP-1 cell line. Niclosamide dose dependently reduced 12Z viability, reduced STAT3 and NF${\rm \small K}$B activity, and increased both cleaved caspase-3 and cleaved PARP. To model the inflammatory microenvironment in endometriotic lesions, we exposed 12Z cells to macrophage conditioned media (CM). Macrophages were differentiated from THP-1 cells using 12-O-tetradecanoylphorbol-13-acetate as M0, and then M0 macrophages were polarized into M1 or M2 using LPS/IFNγ or IL4/IL13, respectively. Conditioned media from M0, M1, or M2 cultures increased 12Z viability. This effect was blocked by niclosamide, and cell viability returned to that of CM from cells treated with niclosamide alone. To assess proteins targeted by niclosamide in 12Z cells, CM from 12Z cells cultured with M0, M1, or M2 with/without niclosamide were analyzed by cytokine/chemokine protein array kits. Conditioned media from M0, M1, and/or M2 stimulated the secretion of cytokines/chemokines from 12Z cells. Production of most of these secreted cytokines/chemokines in 12Z cells was inhibited by niclosamide. Knockdown of each gene in 12Z cells using siRNA resulted in reduced cell viability. These results indicate that niclosamide can inhibit the inflammatory factors in endometriotic epithelial cells stimulated by macrophages by targeting STAT3 and/or NF${\rm \small K}$B signaling.

My notes (saved in your browser only)

Condition tags

mesh:D004716endometriosischronic_pelvic_paininfertility

MeSH descriptors

Endometritis Gene Expression Regulation Inflammation Macrophages Monocytes Niclosamide Anticestodal Agents Anticestodal Agents Cell Communication Cell Line Cell Survival Cell Survival Down-Regulation Endometritis Epithelial Cells Female Gene Expression Regulation Humans Inflammation Macrophages

Citation neighborhood

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.

References (100)

Cited by (17)

Source provenance

europepmc
last seen: 2026-08-22T06:09:51.966504+00:00
openalex
last seen: 2026-06-10T17:14:06.276822+00:00
pubmed
last seen: 2026-05-13T22:19:31.300640+00:00
License: CC0 · commercial use OK