Decreased immediate inflammatory gene induction in activating transcription factor-2 mutant mice

Andreas M. Reimold, James Kim, Robert Finberg, Laurie H. Glimcher

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

Transcription factor activating transcription factor (ATF)-2 is activated by inflammatory signals transduced by the JNK and p38 MAP kinase pathways. To better define the role of ATF-2 in inflammation, adult mice expressing small amounts of a mutant ATF-2 protein were challenged with lipopolysaccharide (LPS), anti-CD3 antibody or virus. Within 3 h of challenge by LPS, ATF-2 mutant mice had decreased induction of the adhesion molecules E-selectin, P-selectin and VCAM-1 as well as the cytokines tumor necrosis factor-α, IL-1β and IL-6 compared with control mice. Stimulation of T lymphocytes by anti-CD3 antibody also showed less induction of IL-1 and IL-6 in ATF-2 mutant tissues. ATF-2 mutant thymocytes treated with anti-CD3 antibody in vitro demonstrated reduced induction of c-Jun, JunB, JunD and Fra-2. However, similar to what was observed after p38 kinase inhibition in normal mice, relative ATF-2 deficiency did not prevent the development of a mononuclear cell infiltrate in the week following an inflammatory stimulus. ATF-2 mutant mice proved more susceptible to death than control mice from LPS plus D-galactosamine injection or Coxsackievirus B3 infection and had a higher incidence of mononuclear pulmonary infiltrates after exposure to Herpes simplex virus-1. ATF-2 is essential for maximal immediate induction of adhesion molecules and cytokine genes, but at later time points may even protect against overactive immune responses.

Original languageEnglish (US)
Pages (from-to)241-248
Number of pages8
JournalInternational Immunology
Volume13
Issue number2
DOIs
StatePublished - Jan 1 2001

Keywords

  • Cytokines
  • Gene regulation
  • In vivo animal models
  • Inflammation
  • Transcription factors

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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