The role of p38 MAPK in rhinovirus-induced monocyte chemoattractant protein-1 production by monocytic-lineage cells.
Viral respiratory infections are a major cause of asthma exacerbations and can contribute to the pathogenesis of asthma. Major group human rhinovirus enters cells by binding to the cell surface molecule ICAM-1 that is present on epithelial and monocytic lineage cells. The focus of the resulting viral infection is in bronchial epithelia. However, previous studies of the cytokine dysregulation that follows rhinovirus infection have implicated monocytic lineage cells in establishing the inflammatory environment even though productive infection is not a result. We have determined that human alveolar macrophages and human peripheral blood monocytes release MCP-1 upon exposure to human rhinovirus 16 (HRV16). Indeed, we have found p38 MAPK activation in human alveolar macrophages within 15 min of exposure to HRV16, and this activation lasts up to 1 h. The targets of p38 MAPK activation include transcriptional activators of the MCP-1 promoter. The transcription factor ATF-2, a p38 MAPK substrate, is phosphorylated 45 min after HRV16 exposure. Furthermore, IkappaBalpha, the inhibitor of the transcription factor NF-kappaB, is degraded. Prevention of HRV16 binding was effective in blocking p38 MAPK activation, ATF-2 phosphorylation, and MCP-1 release. This is the first report of a relationship between HRV16 exposure, MCP-1 release and monocytic-lineage cells suggesting that MCP-1 plays a role in establishing the inflammatory microenvironment initiated in the human airway upon exposure to rhinovirus.
Hall
David J
DJ
Department of Chemistry, Lawrence University, Appleton, WI 54912, USA. halld@lawrence.edu
Bates
Mary Ellen
ME
Guar
Lasya
L
Cronan
Mark
M
Korpi
Nichole
N
Bertics
Paul J
PJ
D051698:Activating Transcription Factor 2; D019138:Antibodies, Blocking / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D019070:Cell Lineage / Q000276:immunology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000037:antagonists & inhibitors / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D020672:I-kappa B Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism; D007555:Isoxazoles / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism / Q000821:virology; D009000:Monocytes / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D000072000:NF-KappaB Inhibitor alpha; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D012229:Rhinovirus / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*
C497105:ATF2 protein, human; D051698:Activating Transcription Factor 2; D019138:Antibodies, Blocking; D000998:Antiviral Agents; D018932:Chemokine CCL2; D017362:Cyclic AMP Response Element-Binding Protein; D020672:I-kappa B Proteins; D007555:Isoxazoles; C000606204:NFKBIA protein, human; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D014157:Transcription Factors; D018799:Intercellular Adhesion Molecule-1; D000072000:NF-KappaB Inhibitor alpha; C059730:Win 52035; D048051:p38 Mitogen-Activated Protein Kinases