In vivo role of p38 mitogen-activated protein kinase in mediating the anti-inflammatory effects of CPG oligodeoxynucleotide in murine asthma

Barun K. Choudhury, James S. Wild, Rafeul Alam, Dennis M. Klinman, Istvan Boldogh, Nilesh Dharajiya, William J. Mileski, Sanjiv Sur

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

DNA containing unmethylated CpG motifs is intrinsically immunostimulatory, inducing the production of a variety of cytokines and chemokines by immune cells. The strong Th1 response triggered by CpG oligodeoxynucleotide (ODN) inhibits the development of Th2-mediated allergic asthma in mice. This work documents that CpG ODN-induced IL-12 production plays a critical role in this process, because intrapulmonary CpG ODN inhibits allergic inflammation in wild-type but not IL-12-/- mice. CpG ODN rapidly localized to alveolar macrophages (AM), thereby triggering the phosphorylation of p38 mitogen-activated protein kinase (MAP kinase). AM cultured with CpG but not control ODN up-regulated IL-12 p40 expression and release, and these effects were blocked by the highly specific p38 MAP kinase inhibitor SB202190. Intrapulmonary administration of this inhibitor blocked the ability of CpG ODN to produce IL-12 in the lungs and reversed the anti-inflammatory effects of CpG ODN on allergic lung inflammation. These findings indicate that IL-12 production by AM is stimulated by intrapulmonary CpG ODN administration through a p38 MAP kinase-dependent process, and IL-12 is a key cytokine that mediates CpG ODN-induced protection against allergic lung inflammation.

Original languageEnglish (US)
Pages (from-to)5955-5961
Number of pages7
JournalJournal of Immunology
Volume169
Issue number10
DOIs
StatePublished - Nov 15 2002

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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