Mol. Hum. Reprod. Advance Access originally published online on May 24, 2007
Molecular Human Reproduction 2007 13(8):595-604; doi:10.1093/molehr/gam032
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Human chorionic gonadotrophin attenuates NF-
B activation and cytokine expression of endometriotic stromal cells
Department of Obstetrics and Gynecology, Medical University of Vienna, AKH, Waehringer Guertel 18-20, A-1090 Vienna, Austria
1 Correspondence address. Tel: +43-1-40400-2842; Fax: +43-1-40400-7842; E-mail: martin.knoefler{at}meduniwien.ac.at
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-
B and expression of two nuclear factor kappa B (NF-B)-inducible genes, tumour necrosing factor (TNF-
) and interleukin (IL)-1ß, 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-- or IL-1ß-induced NF-B DNA-binding activity, whereas another urinary hCG preparation (hCG-B) was less effective. Recombinant hCG or epidermal growth factor (EGF), a contaminant of some urinary hCG preparations, did not alter cytokine-dependent NF-B activation. Immunofluorescene of its p65 subunit revealed that pre-incubation with hCG-A strongly decreased TNF--dependent nuclear expression of NF-B. Accordingly, hCG-A diminished IL-1ß-induced TNF- transcript levels and protein release measured by quantitative real-time PCR and enzyme-linked immunosorbent assay. The hormone also attenuated TNF--dependent mRNA expression of IL-1ß. Western blot analyses revealed that hCG-A impaired TNF--mediated phosphorylation and degradation of the inhibitor IB suggesting that the hormone may reduce nuclear import of NF-B by stabilizing its inhibitor. The data suggest that hCG attenuates inflammation-dependent NF-B activation and cytokine expression that could provide one explanation for the beneficial role of the hormone in endometriotic patients.
Key words:
human endometriotic stromal cells/chorionic gonadotrophin/NF-B/cytokine expression
Submitted on January 18, 2007; resubmitted on March 23, 2007; accepted on March 26, 2007.
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