TNFα-mediated Hsd11b1 binding of NF-κB p65 is associated with suppression of 11β-HSD1 in muscle

Doig, CL ORCID: https://orcid.org/0000-0001-9694-4230, Bashir, J, Zielinska, AE, Cooper, MS, Stewart, PM and Lavery, GG ORCID: https://orcid.org/0000-0001-5794-748X, 2014. TNFα-mediated Hsd11b1 binding of NF-κB p65 is associated with suppression of 11β-HSD1 in muscle. Journal of Endocrinology, 220 (3), pp. 389-396. ISSN 0022-0795

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Abstract

The activity of the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which converts inactive cortisone (11-dehydrocorticosterone (11-DHC)) (in mice) into the active glucocorticoid (GC) cortisol (corticosterone in mice), can amplify tissue GC exposure. Elevated TNFα is a common feature in a range of inflammatory disorders and is detrimental to muscle function in diseases such as rheumatoid arthritis and chronic obstructive pulmonary disease. We have previously demonstrated that 11β-HSD1 activity is increased in the mesenchymal stromal cells (MSCs) by TNFα treatment and suggested that this is an autoregulatory anti-inflammatory mechanism. This upregulation was mediated by the P2 promoter of the Hsd11b1 gene and was dependent on the NF-κB signalling pathway. In this study, we show that in contrast to MSCs, in differentiated C2C12 and primary murine myotubes, TNFα suppresses Hsd11b1 mRNA expression and activity through the utilization of the alternative P1 promoter. As with MSCs, in response to TNFα treatment, NF-κB p65 was translocated to the nucleus. However, ChIP analysis demonstrated that the direct binding was seen at position −218 to −245 bp of the Hsd11b1 gene's P1 promoter but not at the P2 promoter. These studies demonstrate the existence of differential regulation of 11β-HSD1 expression in muscle cells through TNFα/p65 signalling and the P1 promoter, further enhancing our understanding of the role of 11β-HSD1 in the context of inflammatory disease.

Item Type:	Journal article
Publication Title:	Journal of Endocrinology
Creators:	Doig, C.L., Bashir, J., Zielinska, A.E., Cooper, M.S., Stewart, P.M. and Lavery, G.G.
Publisher:	Bioscientifica
Date:	March 2014
Volume:	220
Number:	3
ISSN:	0022-0795
Identifiers:	Number Type 10.1530/JOE-13-0494 DOI 2554885 Other
Rights:	© 2014 The authors. This work is licensed under a Creative Commons Attribution 3.0 Unported License: https://creativecommons.org/licenses/by/3.0/
Divisions:	Schools > School of Science and Technology
Record created by:	Melissa Cornwell
Date Added:	20 Jan 2026 14:40
Last Modified:	20 Jan 2026 14:40
URI:	https://irep.ntu.ac.uk/id/eprint/55086

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