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Regulation of T cell‐dependent and ‐independent IL‐12 production by the three Th2‐type cytokines IL‐10, IL‐6, and IL‐4
Author(s) -
Takenaka Hiroshi,
Maruo Seiji,
Yamamoto Norihiko,
Wysocka Maria,
Ono Shiro,
Kobayashi Michiko,
Yagita Hideo,
Okumura Ko,
Hamaoka Toshiyuki,
Trinchieri Giorgio,
Fujiwara Hiromi
Publication year - 1997
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.61.1.80
Subject(s) - biology , immunology , interleukin 4 , t cell , interleukin , cytokine , microbiology and biotechnology , immune system
The production of IL‐12 by macrophages/dendritic cells (M ɸ /DC) is mediated either by a T cell‐dependent pathway that is induced primarily by the interaction of CD40 ligand (CD40L) on activated T cells with CD40 on IL‐12‐producing cells or by a T cell‐independent pathway that is induced by bacteria or bacterial products and enhanced by interferon‐γ (IFN‐γ). In this study we investigated the ability of the Th2‐type cytokines interleukin (IL) ‐10, IL‐6, and IL‐4 to modulate IL‐12 production in M ɸ /DC induced through the two pathways. IL‐12 production was induced in M ɸ /DC from normal mice by stimulation with the combination of IFN‐γ plus lipopolysaccharide (LPS) or Staphylococcus aureus Cowan I (a model for the T cell‐independent pathway) or by co‐culture with Chinese hamster ovary (CHO) cells transfected with the CD40L (a model for the T cell‐dependent pathway). The effects of three Th2‐type cytokines on IL‐12 production by M ɸ /DC through the two pathways were examined. IL‐10 inhibited IL‐12 production induced through both pathways, although the inhibitory effect was more potent on the (IFN‐γ + LPS)‐induced pathway. IL‐6 inhibited only (LPS + IFN‐γ)‐induced IL‐12 production. The effect of IL‐4 was particularly noteworthy: this cytokme inhibited (LPS + IFN‐γ)‐induced IL‐12 production, whereas it potentiated the production of IL‐12 induced by CD40L. Regulation of IL‐12 protein production by IL‐10 and IL‐4 was found to correspond to the levels of mRNA accumulation for the p40 and p35 IL‐12 genes, whereas the presence of IL‐6 during stimulation decreased IL‐12 protein production without affecting steady‐state mRNA levels. These results indicate that IL‐12 production in M ɸ /DC induced through a T cell‐dependent or ‐independent pathway is positively or negatively regulated by particular cytokines at various control levels. J. Leukoc. Biol . 61: 80–87; 1997.