The p38 mitogen-activated protein kinase is required for IL-12-induced IFN-γ expression

Shangming Zhang, Mark Kaplan

Research output: Contribution to journalArticle

97 Citations (Scopus)

Abstract

IL-12 is a central immunoregulatory cytokine that promotes cell-mediated immune responses and the differentiation of naive CD4+ cells into Th1 cells. We and others have demonstrated that the Stat4 is critical for IFN-γ production by activated T cells and Th1 cells. However, several studies have suggested that other pathways may be involved in IL-12-stimulated IFN-γ expression. In this report we demonstrate that IL-12 activates mitogen- activated protein kinase kinase 3/6 (MKK) and p38 mitogen-activated protein kinase (MAPK), but not p44/42 (ERK) or stress-activated protein kinase/c-Jun N-terminal kinase MAPK. The activation of p38 MAPK is required for normal induction of IFN-γ mRNA and IFN-γ secretion by IL-12 in activated T cells and Th1 cells. Importantly, IL-12-stimulated p38 MAPK effector functions occur through a Stat4-independent mechanism and correlate with increased serine phosphorylation of activating transcription factor-2. The requirement for p38 MAPK in IL-12 function suggests that this pathway may be an important in vivo target for the anti-inflammatory actions of p38 MAPK inhibitors.

Original languageEnglish
Pages (from-to)1374-1380
Number of pages7
JournalJournal of Immunology
Volume165
Issue number3
StatePublished - Aug 1 2000

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p38 Mitogen-Activated Protein Kinases
Interleukin-12
Th1 Cells
MAP Kinase Kinase 6
Activating Transcription Factor 2
MAP Kinase Kinase 3
T-Lymphocytes
JNK Mitogen-Activated Protein Kinases
Protein Kinase Inhibitors
Heat-Shock Proteins
Mitogen-Activated Protein Kinases
Protein Kinases
Serine
Anti-Inflammatory Agents
Phosphorylation
Cytokines
Messenger RNA

ASJC Scopus subject areas

  • Immunology

Cite this

The p38 mitogen-activated protein kinase is required for IL-12-induced IFN-γ expression. / Zhang, Shangming; Kaplan, Mark.

In: Journal of Immunology, Vol. 165, No. 3, 01.08.2000, p. 1374-1380.

Research output: Contribution to journalArticle

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