Oncostatin M causes eotaxin-1 release from airway smooth muscle: Synergy with IL-4 and IL-13

• Published in: Journal of Allergy and Clinical Immunology Vol. 115; no. 3; pp. 514 - 520
• Main Authors: Faffe, Débora S., Flynt, Lesley, Mellema, Matthew, Moore, Paul E., Silverman, Eric S., Subramaniam, Venkat, Jones, Matthew R., Mizgerd, Joseph P., Whitehead, Timothy, Imrich, Amy, Panettieri, Reynold A., Shore, Stephanie A.
• Format: Journal Article
• Language: English
• Published: United States Mosby, Inc 01.03.2005; Elsevier Limited
• Subjects: Asthma; Blotting, Western; c-Jun N-terminal kinase; Chemokine CCL11; Chemokines, CC - immunology; Chemokines, CC - secretion; Cytokines; DNA-Binding Proteins - drug effects; DNA-Binding Proteins - immunology; DNA-Binding Proteins - metabolism; Drug Synergism; Enzyme-Linked Immunosorbent Assay; Experiments; extracellular signal-regulated kinase; Flow Cytometry; Growth Inhibitors - pharmacology; Humans; IL-4Rα; Interleukin-13 - immunology; Interleukin-13 - metabolism; Interleukin-4 - immunology; Interleukin-4 - metabolism; Kinases; Lung - drug effects; Lung - immunology; Lung - metabolism; Mitogen-Activated Protein Kinases - drug effects; Mitogen-Activated Protein Kinases - immunology; Mitogen-Activated Protein Kinases - metabolism; monocyte chemoattractant protein 1; Muscle, Smooth - drug effects; Muscle, Smooth - immunology; Muscle, Smooth - metabolism; Muscular system; Oncostatin M; Peptides - pharmacology; Phosphorylation; Proteins; Receptors, Interleukin-4 - drug effects; Receptors, Interleukin-4 - immunology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Rodents; Signal transducer and activator of transcription 3; Smooth muscle; STAT3 Transcription Factor; Trans-Activators - drug effects; Trans-Activators - immunology; Trans-Activators - metabolism; Vascular endothelial growth factor; STAT-3-WT; c-Jun N-terminal kinase; extracellular signal-regulated kinase; CNTF; MCP-1; JNK; VEGF; OSM; OSMR; HASM; STAT; JAK; vascular endothelial growth factor; Signal transducer and activator of transcription 3; monocyte chemoattractant protein 1; STAT-3F; STAT-3-C; GAPDH; IL-4Rα; ERK
• ISSN: 0091-6749; 1097-6825; 1365-2567
• DOI: 10.1016/j.jaci.2004.11.033

Eotaxin is implicated in asthmatic eosinophilia. Oncostatin M (OSM) causes eotaxin release from fibroblasts. We sought to examine the effects and mechanism of action of OSM and other IL-6 family cytokines on eotaxin release from human airway smooth muscle cells. Eotaxin 1 release was measured by means of ELISA. Western blotting was used to examine mitogen-activated protein kinase and signal transducer and activator of transcription 3 (STAT-3) phosphorylation. Eotaxin promoter activity was analyzed in cells transfected with wild-type STAT-3, a mutant form of STAT-3 that cannot be phosphorylated, and a constitutively active form of STAT-3. The mRNA and protein expression of IL-4Rα, the signaling receptor for IL-4 and IL-13, was evaluated by means of real-time PCR and flow cytometry, respectively. OSM increased eotaxin 1 release and augmented IL-4– or IL-13–induced eotaxin release, whereas other IL-6 family cytokines did not. OSM caused a greater increase in STAT-3 phosphorylation and STAT-3–mediated gene transcription than other IL-6 family cytokines. OSM increased eotaxin promoter activity and augmented IL-13– and IL-4–induced increases in promoter activity. The constitutively active form of STAT-3 increased eotaxin promoter activity, whereas the mutant form of STAT-3 that cannot be phosphorylated significantly reduced eotaxin promoter activity induced by OSM or IL-4 plus OSM. OSM increased IL-4Rα mRNA and protein levels. OSM induces eotaxin 1 expression in human airway smooth muscle cells by a mechanism involving STAT-3. OSM synergizes with IL-13 and IL-4 to increase eotaxin 1 expression, possibly as a result of effects on IL-4Rα expression.