Retinoids inhibit interleukin-12 production in macrophages through physical associations of retinoid X receptor and NFκB

Soon Young Na, Bok Yun Kang, Su Wol Chung, Su Ji Han, Xiaojing Ma, Giorgio Trinchieri, Suhn Young Im, Jae Woon Lee, Tae Sung Kim

Research output: Contribution to journalArticle

202 Citations (Scopus)

Abstract

Lipopolysaccharide (LPS) increases the production of interleukin-12 (IL- 12) from mouse macrophages via a κB site within the IL-12 p40 promoter. In this study, we found that retinoids inhibit this LPS-stimulated production of IL-12 in a dose-dependent manner. The NFκB components p50 and p65 bound retinoid X receptor (RXR) in a ligand-independent manner in vitro, and the interaction interfaces involved the p50 residues 1-245, the p65 residues 194- 441, and the N-terminal A/B/C domains of RXR. Activation of macrophages by LPS resulted in markedly enhanced binding activities to the κB site, which significantly decreased upon addition of retinoids, as demonstrated by the electrophoretic mobility shift assays. In cotransfections of CV-1 and HeLa cells, RXR also inhibited the NFκB transactivation in a ligand-dependent manner, whereas a mutant RXR lacking the AF2 transactivation domain, which serves as ligand-dependent binding sites for transcription integrators SRC-1 and p300, was without any effect. In addition, coexpression of increasing amounts of SRC-1 or p300 relieved the retinoid-mediated inhibition of the NFκB transactivation. From these results, we propose that retinoid-mediated suppression of the IL-12 production from LPS-activated macrophages may involve both inhibition of the NFκB-DNA interactions and competitive recruitment of transcription integrators between NFκB and RXR.

Original languageEnglish
Pages (from-to)7674-7680
Number of pages7
JournalJournal of Biological Chemistry
Volume274
Issue number12
DOIs
Publication statusPublished - 1999 Mar 19
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

Fingerprint Dive into the research topics of 'Retinoids inhibit interleukin-12 production in macrophages through physical associations of retinoid X receptor and NFκB'. Together they form a unique fingerprint.

  • Cite this