c-Jun NH2-terminal kinase regulates lipopolysaccharide-induced pulmonary mononuclear cell recruitment via CCL2.
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 NH(2)-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.
Young
Scott K
SK
Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado, USA.
Arndt
Patrick G
PG
D000818:Animals; D018932:Chemokine CCL2 / Q000172:deficiency / Q000276:immunology*; D005260:Female; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020556:Neutrophil Infiltration / Q000276:immunology*; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D008070:Lipopolysaccharides; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases