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 Lee, Tae Sung Kim

Research output: Contribution to journalArticle

198 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 (US)
Pages (from-to)7674-7680
Number of pages7
JournalJournal of Biological Chemistry
Volume274
Issue number12
DOIs
StatePublished - Mar 19 1999
Externally publishedYes

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Retinoid X Receptors
Macrophages
Retinoids
Interleukin-12
Lipopolysaccharides
Transcriptional Activation
Transcription
Ligands
Electrophoretic mobility
Macrophage Activation
Electrophoretic Mobility Shift Assay
HeLa Cells
Assays
Chemical activation
Binding Sites
DNA

ASJC Scopus subject areas

  • Biochemistry

Cite this

Retinoids inhibit interleukin-12 production in macrophages through physical associations of retinoid X receptor and NFκB. / Na, Soon Young; Kang, Bok Yun; Chung, Su Wol; Han, Su Ji; Ma, Xiaojing; Trinchieri, Giorgio; Im, Suhn Young; Lee, Jae; Kim, Tae Sung.

In: Journal of Biological Chemistry, Vol. 274, No. 12, 19.03.1999, p. 7674-7680.

Research output: Contribution to journalArticle

Na, Soon Young ; Kang, Bok Yun ; Chung, Su Wol ; Han, Su Ji ; Ma, Xiaojing ; Trinchieri, Giorgio ; Im, Suhn Young ; Lee, Jae ; Kim, Tae Sung. / Retinoids inhibit interleukin-12 production in macrophages through physical associations of retinoid X receptor and NFκB. In: Journal of Biological Chemistry. 1999 ; Vol. 274, No. 12. pp. 7674-7680.
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