Retinoic acid inhibits inducible nitric oxide synthase expression in 3T3-L1 adipocytes.
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.
Yang
Jeong-Yeh
JY
Department of Biochemistry and Institute for Medical Sciences, Medical School, Chonbuk National University, Jeonju 561-756, Korea.
Koo
Bon-Sun
BS
Kang
Mi-Kyung
MK
Rho
Hye-Won
HW
Sohn
Hee-Sook
HS
Jhee
Eun-Chung
EC
Park
Jin-Woo
JW
D016475:3T3 Cells; D017667:Adipocytes / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008071:Lipoprotein Lipase / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D014212:Tretinoin / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D004791:Enzyme Inhibitors; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D014212:Tretinoin; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D008071:Lipoprotein Lipase