Thyroid-stimulating hormone induces interleukin-6 release from human adipocytes through activation of the nuclear factor-kappaB pathway.
Our objective was to identify the signaling pathway activated by TSH that induces IL-6 secretion from human abdominal sc differentiated adipocytes. Human abdominal sc preadipocytes in culture were differentiated into adipocytes. IL-6 release stimulated by TSH was inhibited by 35% (P < 0.05) with SN50, an inhibitor of nuclear factor-kappaB (NF-kappaB) nuclear translocation, and 60% (P < 0.01) with sc-514, an inhibitor of inhibitory-kappaB (IkappaB) kinase (IKK)-beta. Phosphorylation of IKKbeta increased upon TSH treatment (10.3-fold, P < 0.01), and IkappaBalpha levels were reduced by 78% (P < 0.01). TSH activated NF-kappaB (23-fold, P < 0.001), a process that was inhibited (60%, P < 0.01) by SN50. Inhibition of protein kinase A by H89 did not affect TSH-stimulated IKKbeta phosphorylation or IkappaBalpha degradation. TSH-mediated NF-kappaB activation and IL-6 induction also specifically occurred in Chinese hamster ovarian cells expressing the human TSH receptor, resulting in a 5.9-fold (P < 0.001) increase in IKKbeta phosphorylation and a 9.5-fold increase in IL-6 mRNA expression. Our data demonstrate that the IKKbeta/NF-kappaB pathway is a novel TSH target that is required for TSH-induced IL-6 release from human adipocytes.
Antunes
Tayze T
TT
Department of Medicine, University of Ottawa, Chronic Disease Program, Ottawa Health Research Institute, Ottawa Ontario, Canada K1Y 4E9.
Gagnon
AnneMarie
A
Langille
Melanie L
ML
Sorisky
Alexander
A
D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D016466:CHO Cells; D018929:Cell Culture Techniques; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D007700:Kinetics; D016328:NF-kappa B / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D013972:Thyrotropin / Q000494:pharmacology*
D015850:Interleukin-6; D016328:NF-kappa B; D013972:Thyrotropin