Retinoic acid inhibits inducible nitric oxide synthase expression in 3T3-L1 adipocytes.
- Author:
Jeong Yeh YANG
1
;
Bon Sun KOO
;
Mi Kyung KANG
;
Hye Won RHO
;
Hee Sook SOHN
;
Eun Chung JHEE
;
Jin Woo PARK
Author Information
1. Department of Biochemisty and Institute for Medical Sciences Medical School, Korea. jinwoo@moak.chonbuk.ac.kr
- Publication Type:Original Article
- Keywords:
adipocytes;
retinoic acid receptors;
nitric oxide;
nitric oxide synthase;
tretinoin;
tumor necroses factor
- MeSH:
3T3 Cells;
Adipocytes/drug effects/*enzymology/metabolism;
Animals;
Cells, Cultured;
Enzyme Induction/drug effects;
Enzyme Inhibitors/pharmacology;
Lipoprotein Lipase/drug effects/metabolism;
Mice;
NF-kappa B/antagonists & inhibitors;
Nitric Oxide/metabolism;
Nitric-Oxide Synthase/*antagonists & inhibitors/*metabolism;
Tretinoin/*pharmacology;
Tumor Necrosis Factor/pharmacology
- From:Experimental & Molecular Medicine
2002;34(5):353-360
- CountryRepublic of Korea
- Language:English
-
Abstract:
The present study was undertaken to explore whether retinoids, which are known to have immunomodulatory actions, could attenuate tumor necrosis factor-alpha (TNF)-stimulated inducible nitric oxide synthase (iNOS) expression in 3T3-L1 adipocytes. Adipocytes incubated with TNF induced dose- and time-dependent accumulation of nitrite in the culture medium through the iNOS induction as confirmed by Western blotting. Treatment of cells with TNF in the presence of all-trans-retinoic acid (RA) significantly decreased their ability to produce nitrite and iNOS induction. Both 13-cis- and all- trans-RA-induced suppression was dose-dependent, and all-trans-RA was somewhat potent than 13-cis-RA. The inhibitory effect of RA on TNF-induced iNOS induction was reversible, completely recovered after 2 days, and was exerted through the inhibition of NF-kappaB activation. TNF also suppressed the lipoprotein lipase (LPL) activity of 3T3-L1 adipocytes. RA could not reverse the TNF- induced LPL suppression at RA levels causing near complete inhibition of the TNF-induced NO production. These results indicate that RAs attenuate iNOS expression reversibly in TNF-stimulated 3T3-L1 adipocytes, and that the TNF- induced LPL suppression is not the result of NO overproduction.
