Nuclear factor-kappa B signaling in endometriotic stromal cells is not inhibited by progesterone owing to an aberrant endoplasmic reticulum stress response: a possible role for an altered inflammatory process in endometriosis

Choi J, JongYeob Choi, Jo M, MinWha Jo, Eunyoung Lee, Lee E, Dong‐Yun Lee, Lee DY, Dong-Yun Lee, DooSeok Choi, Choi D
Molecular human reproduction · 2021 · vol. 27(2) · doi:10.1093/molehr/gaab002 · PMID:33507306 · W3121618927
Lab / animal OA: bronze CC0 ⤵ 12 in-corpus citations
📄 Open PDF View on OpenAlex View on PubMed View at publisher
⚙ AI-generated summary by gemini-2.5-flash-lite, 2026-06-07 ⓘ

Progesterone resistance in endometriotic stromal cells is linked to an aberrant endoplasmic reticulum stress response, preventing inhibition of nuclear factor-kappa B and increasing pro-inflammatory cytokine production.

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

Abstract

Endoplasmic reticulum (ER) stress serves as a key modulator of the inflammatory response by controlling nuclear factor-kappaB (NF-κB) signaling. Previous studies from our laboratory have reported an abnormal induction of ER stress linked to progesterone resistance in human endometriotic cells. Therefore, an aberrant ER stress response to progesterone might contribute to the altered inflammatory response observed in endometriotic tissues. To evaluate this hypothesis, we investigated whether ER stress is involved in regulation of NF-κB in endometrial stromal cells and whether induction of aberrant ER stress in endometriotic stromal cells affects pro-inflammatory cytokine production. We found that tunicamycin-induced ER stress inhibited NF-κB activation and pro-inflammatory cytokine (IL-6 and COX2) production in TNF-α- or IL-1β-treated normal endometrial stromal cells (NECSs). Tunicamycin increased the expression of A20 and C/EBPβ, which are negative regulators of NF-κB, and this increase inhibited NF-κB activity in NESCs incubated with TNF-α or IL-1β. Similarly, progesterone increased A20 and C/EBPβ expression through upregulation of ER stress in NESCs, resulting in inhibition of NF-κB activity and IL-6 and COX2 production. However, progesterone had no significant effects on induction of ER stress, A20 or C/EBPβ expression, NF-κB activity or IL-6 or COX2 production in ovarian endometriotic cyst stromal cells (ECSCs). In contrast, upregulation of ER stress by tunicamycin significantly reduced IL-6 and COX2 production by inhibiting NF-κB activity in ECSCs. In conclusion, our results suggest that NF-κB activity in endometriotic stromal cells was not inhibited because of an aberrant ER stress response to progesterone, resulting in an increase in pro-inflammatory cytokine production.

My notes (saved in your browser only)

Condition tags

endometriosis

MeSH descriptors

Endometriosis Endometrium Endoplasmic Reticulum Stress NF-kappa B Progesterone Stromal Cells Case-Control Studies Case-Control Studies CCAAT-Enhancer-Binding Protein-beta CCAAT-Enhancer-Binding Protein-beta CCAAT-Enhancer-Binding Protein-beta Cells, Cultured Cells, Cultured Cyclooxygenase 2 Cyclooxygenase 2 Cyclooxygenase 2 Cytokines Cytokines Cytokines Endometriosis

Citation neighborhood (2-hop)

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. Outer rings show 2-hop neighbours — papers reached through the immediate citers/citees. [ collapse to 1-hop ]

References (54)

Cited by (13)

Source provenance

europepmc
last seen: 2026-10-18T09:30:06.152893+00:00
openalex
last seen: 2026-06-10T17:14:06.276822+00:00
pubmed
last seen: 2026-10-08T21:29:46.384990+00:00
License: CC0 · commercial use OK