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

52 Citations (Scopus)

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
StatePublished - 2001

Fingerprint

Activating Transcription Factor 2
Genes
Lipopolysaccharides
Anti-Idiotypic Antibodies
Interleukin-1
Interleukin-6
Coxsackievirus Infections
Cytokines
Galactosamine
P-Selectin
E-Selectin
Vascular Cell Adhesion Molecule-1
MAP Kinase Signaling System
Human Herpesvirus 1
p38 Mitogen-Activated Protein Kinases
Thymocytes
Mouse Atf2 protein
Transcription Factors
Phosphotransferases
Tumor Necrosis Factor-alpha

Keywords

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

ASJC Scopus subject areas

  • Immunology

Cite this

Decreased immediate inflammatory gene induction in activating transcription factor-2 mutant mice. / Reimold, Andreas M.; Kim, James; Finberg, Robert; Glimcher, Laurie H.

In: International Immunology, Vol. 13, No. 2, 2001, p. 241-248.

Research output: Contribution to journalArticle

Reimold, Andreas M. ; Kim, James ; Finberg, Robert ; Glimcher, Laurie H. / Decreased immediate inflammatory gene induction in activating transcription factor-2 mutant mice. In: International Immunology. 2001 ; Vol. 13, No. 2. pp. 241-248.
@article{8b7979488d5f484988bc5c98823b1727,
title = "Decreased immediate inflammatory gene induction in activating transcription factor-2 mutant mice",
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.",
keywords = "Cytokines, Gene regulation, In vivo animal models, Inflammation, Transcription factors",
author = "Reimold, {Andreas M.} and James Kim and Robert Finberg and Glimcher, {Laurie H.}",
year = "2001",
language = "English (US)",
volume = "13",
pages = "241--248",
journal = "International Immunology",
issn = "0953-8178",
publisher = "Oxford University Press",
number = "2",

}

TY - JOUR

T1 - Decreased immediate inflammatory gene induction in activating transcription factor-2 mutant mice

AU - Reimold, Andreas M.

AU - Kim, James

AU - Finberg, Robert

AU - Glimcher, Laurie H.

PY - 2001

Y1 - 2001

N2 - 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.

AB - 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.

KW - Cytokines

KW - Gene regulation

KW - In vivo animal models

KW - Inflammation

KW - Transcription factors

UR - http://www.scopus.com/inward/record.url?scp=0035140889&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035140889&partnerID=8YFLogxK

M3 - Article

VL - 13

SP - 241

EP - 248

JO - International Immunology

JF - International Immunology

SN - 0953-8178

IS - 2

ER -