Nuclear factor κB pathway and interleukin-6 are affected in eutopic endometrium of women with endometriosis

Carlos Ponce, Carlos R. Ponce, Marisa Torres, M.J. Torres, Carolina Galleguillos, Hugo Sovino, M A Boric, M Angélica Boric, Ariel Fuentes, Marı́a Cecilia Johnson, M Cecilia Johnson
Reproduction (Cambridge, England) · 2009 · vol. 137(4) , pp. 727–737 · doi:10.1530/rep-08-0407 · PMID:19129371 · W2145104679
article OA: bronze CC0 ⤵ 45 in-corpus citations
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Eutopic endometrium from endometriosis patients shows decreased IL6, NFKBIA, and CHUK expression during the late secretory phase, indicating deregulation of the canonical NFKB pathway.

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Abstract

In order to investigate the role of the nuclear factor kappaB (NFKB) pathway on gene expression in the eutopic endometrium in endometriosis, and in particular of interleukin-6 (IL6), we evaluated RELA, IkappaB kinase (CHUK), NFKBIA and IL6 expressions and NFKB DNA binding in eutopic endometrium from women with endometriosis. Eutopic endometrium was obtained from 37 women with endometriosis and 42 fertile women during laparoscopy. We analysed RELA, CHUK, NFKBIA and IL6 mRNA levels (RT-PCR); RELA, CHUK and NFKBIA proteins and p-NFKBIA/NFKBIA ratio (western blot); and NFKB binding (DNA shift assay) and IL6 concentration (ELISA) in endometrial explants. Our results indicate that mRNA and cytoplasmic proteins of RELA and CHUK exhibit constant levels in normal endometrium during the menstrual cycle. A dramatic increase (P<0.05) in NFKBIA mRNA expression, RELA nuclear presence and the mRNA and the protein of IL6 during late secretory phase was also observed in this tissue. By contrast, in eutopic endometrium from endometriosis patients, a decrease (P<0.05) in IL6 mRNA and protein (61%), NFKBIA mRNA (46%), p-NFKBIA/NFKBIA ratio (42%), RELA nuclear stromal (68%) and CHUK (48%) proteins were found exclusively during the late secretory phase compared with normal endometrium. In conclusion, the canonical activation of NFKB pathway is deregulated and may have reduced transcriptional function affecting NFKBIA and IL6 expression, genes related local proinflammatory processes. These molecular alterations observed during the late secretory phase in eutopic endometrium from endometriosis patients constitute a NFKB system dysfunction, suggesting that NFKB could be an important factor in endometriosis aetiology.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Endometrium Interleukin-6 NF-kappa B Adult Case-Control Studies DNA DNA Endometriosis Endometrium Female Humans I-kappa B Kinase I-kappa B Kinase I-kappa B Proteins I-kappa B Proteins Interleukin-6 NF-kappa B NF-KappaB Inhibitor alpha RNA, Messenger

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References (72)

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