Retinoid-mediated inhibition of interleukin-12 production in mouse macrophages suppresses Th1 cytokine profile in CD4+ T cells

B. Y. Kang, S. W. Chung, S. H. Kim, S. N. Kang, Y. K. Choe, T. S. Kim

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

1. Interleukin-12 (IL-12) plays a central role in the immune system by driving the immune response towards T helper 1 (Th1) type responses characterized by high IFN-γ and low IL-4 production. In this study we investigated whether retinoid-mediated inhibition of interleukin-12 production in mouse macrophages could regulate cytokine profile of antigen (Ag)-primed CD4+ Th cells. 2. Pretreatment with retinoids (9-cis-RA, all-trans-RA, TTNPB) significantly inhibited IL-12 production by mouse macrophages stimulated with lipopolysaccharide (LPS) or heated-killed Listeria monocytogenes (HKL). Retinoid-pretreated macrophages reduced their ability to induce IFN-γ and increased the ability to induce IL-4 in Ag-primed CD4+ T cells. 3. Addition of recombinant IL-12 to cultures of retinoid-pretreated macrophages and CD4+ T cells restored IFN-γ production in CD4+ T cells. 4. The in vivo administration of 9-cis-RA resulted in the inhibition of IL-12 production by macrophages stimulated in vitro with either LPS or HKL, leading to the inhibition of Th1 cytokine profile (decreased IFN-γ and increased IL-4 production) in CD4+ T cells. 5. These findings may explain some known effects of retinoids including the inhibition of encephalitogenicity, and point to a possible therapeutic use of retinoids in the Th1-mediated immune diseases such as autoimmune diseases.

Original languageEnglish
Pages (from-to)581-586
Number of pages6
JournalBritish Journal of Pharmacology
Volume130
Issue number3
DOIs
Publication statusPublished - 2000

Keywords

  • Cytokine profile
  • Interleukin-12
  • Macrophage
  • Retinoids
  • T helper cell

ASJC Scopus subject areas

  • Pharmacology

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