Retinoid-mediated inhibition of interleukin-12 production in mouse macrophages suppresses Th1 cytokine profile in CD4(+) T cells.
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-gamma 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. 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-gamma and increased the ability to induce IL-4 in Ag-primed CD4(+) T cells. Addition of recombinant IL-12 to cultures of retinoid-pretreated macrophages and CD4(+) T cells restored IFN-gamma production in CD4(+) T cells. 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-gamma and increased IL-4 production) in CD4(+) T cells. 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.
Kang
B Y
BY
College of Pharmacy, Chonnam National University, Kwangju 500-757, Republic of Korea.
Chung
S W
SW
Kim
S H
SH
Kang
S N
SN
Choe
Y K
YK
Kim
T S
TS
D000818:Animals; D000942:Antigens, Bacterial / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D016207:Cytokines / Q000097:blood*; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000494:pharmacology; D015847:Interleukin-4 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008089:Listeria monocytogenes / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D011994:Recombinant Proteins / Q000494:pharmacology; D012176:Retinoids / Q000494:pharmacology*
D000942:Antigens, Bacterial; D016207:Cytokines; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D012176:Retinoids; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma