Human chorionic gonadotrophin attenuates NF-kappaB activation and cytokine expression of endometriotic stromal cells

Huber AV, A V Huber, Anja Huber, Saleh L, Leila Saleh, L Saleh, J Prast, Johanna Prast, Prast J, Peter Haslinger, Haslinger P, P Haslinger, Knöfler M, Martin Knöfler
Molecular human reproduction · 2007 · vol. 13(8) , pp. 595–604 · doi:10.1093/molehr/gam032 · PMID:17525069 · W2114531384
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Human chorionic gonadotrophin preparation hCG-A suppressed TNF-alpha- or IL-1beta-induced NF-kappaB activation and cytokine expression in endometriotic stromal cells by stabilizing IkappaBalpha.

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Abstract

Recently, a clinical study provided evidence that treatment of endometriotic women with human chorionic gonadotrophin (hCG) alleviates disease-related pain and sleeplessness suggesting therapeutic effects of the hormone. Since endometriosis is associated with aberrant concentrations of inflammatory mediators in the peritoneal fluid, we investigated whether hCG may affect cytokine-dependent activation of the key-regulatory transcription factor NF-kappaB and expression of two nuclear factor kappa B (NF-kappaB)-inducible genes, tumour necrosing factor (TNF-alpha) and interleukin (IL)-1beta, in stromal cells isolated from ectopic endometriotic tissues. Electrophoretic mobility shift assay revealed that treatment of these cultures with the urinary preparation hCG-A suppressed TNF-alpha- or IL-1beta-induced NF-kappaB DNA-binding activity, whereas another urinary hCG preparation (hCG-B) was less effective. Recombinant alphahCG or epidermal growth factor (EGF), a contaminant of some urinary hCG preparations, did not alter cytokine-dependent NF-kappaB activation. Immunofluorescene of its p65 subunit revealed that pre-incubation with hCG-A strongly decreased TNF-alpha-dependent nuclear expression of NF-kappaB. Accordingly, hCG-A diminished IL-1beta-induced TNF-alpha transcript levels and protein release measured by quantitative real-time PCR and enzyme-linked immunosorbent assay. The hormone also attenuated TNF-alpha-dependent mRNA expression of IL-1beta. Western blot analyses revealed that hCG-A impaired TNF-alpha-mediated phosphorylation and degradation of the inhibitor IkappaBalpha suggesting that the hormone may reduce nuclear import of NF-kappaB by stabilizing its inhibitor. The data suggest that hCG attenuates inflammation-dependent NF-kappaB activation and cytokine expression that could provide one explanation for the beneficial role of the hormone in endometriotic patients.

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Condition tags

endometriosis

MeSH descriptors

Chorionic Gonadotropin Cytokines Endometriosis NF-kappa B Cells, Cultured Cells, Cultured Chorionic Gonadotropin Chorionic Gonadotropin Cytokines Cytokines Cytokines Cytokines Electrophoretic Mobility Shift Assay Electrophoretic Mobility Shift Assay Endometriosis Endometriosis Female Female Humans Humans

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 (64)

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