C-Jun NH2-terminal kinase regulates lipopolysaccharide-induced pulmonary mononuclear cell recruitment via CCL2

Scott K. Young, Patrick G. Arndt

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Subsequent to the initial recruitment of neutrophils, monocytes are recruited to the lung after an injurious insult. Previously the authors have shown that inhibition of either p38 or c-Jun NH2-terminal kinase (JNK) decreased pulmonary neutrophil recruitment in mice exposed to lipopolysaccharide (LPS). As the signaling pathways regulating the influx of mononuclear cells to the lung are poorly understood, the authors undertook the present study to examine the roles of p38 and JNK. In a model of LPS-induced lung inflammation, systemic inhibition of JNK, but not p38, decreased the recruitment of mononuclear cells to the lung. Levels of CCL2 (monocyte chemoattractant protein 1 [MCP-1]) were decreased in the setting of JNK inhibition, with LPS-induced pulmonary mononuclear cell recruitment in CCL2-deficient mice similar to that found with JNK inhibition. The decrease in LPS-induced CCL2 levels in the lung seen with JNK inhibition, however, was independent of neutrophil recruitment, as systemic depletion of neutrophils had no effect on pulmonary CCL2 levels after LPS exposure. In sum, these results suggest that JNK, but not p38, regulates LPS-induced mononuclear cell recruitment to the lung, that this occurs through a CCL2-dependent pathway, and that LPS-induced pulmonary CCL2 expression is dependent on JNK but independent of pulmonary neutrophil recruitment.

Original languageEnglish (US)
Pages (from-to)682-700
Number of pages19
JournalExperimental Lung Research
Volume35
Issue number8
DOIs
StatePublished - Oct 14 2009

Bibliographical note

Funding Information:
Received 20 November 2008; accepted 26 February 2009. This work was supported by Grant HL-67179 from the National Institutes of Health. Address correspondence to Patrick G. Arndt, MD, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Minnesota, 420 Delaware Street SE, MMC 276, Minneapolis, MN 55455, USA.

Keywords

  • Chemokines
  • Lipopolysaccharide
  • Lung
  • Monocytes/macrophages
  • Protein kinases

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