Oncostatin M regulates eotaxin expression in fibroblasts and eosinophilic inflammation in C57BL/6 mice.
Oncostatin M (OSM) is a member of the IL-6/LIF (or gp130) cytokine family, and its potential role in inflammation is supported by a number of activities identified in vitro. In this study, we investigate the action of murine OSM on expression of the CC chemokine eotaxin by fibroblasts in vitro and on mouse lung tissue in vivo. Recombinant murine OSM stimulated eotaxin protein production and mRNA levels in the NIH 3T3 fibroblast cell line. IL-6 could regulate a small induction of eotaxin in NIH 3T3 cells, but other IL-6/LIF cytokines (LIF, cardiotrophin-1 (CT-1)) had no effect. Cell signaling studies showed that murine OSM, LIF, IL-6, and CT-1 stimulated the tyrosine phosphorylation of STAT-3, suggesting STAT-3 activation is not sufficient for eotaxin induction in NIH 3T3 cells. OSM induced ERK-1,2 and p38 mitogen-activated protein kinase phosphorylation in NIH 3T3 cells, and inhibitors of ERK (PD98059) or p38 (SB203580) could partially reduce OSM-induced eotaxin production, suggesting partial dependence on mitogen-activated protein kinase signaling. OSM (but not LIF, IL-6, or CT-1) also induced eotaxin release by mouse lung fibroblast cultures derived from C57BL/6 mice. Overexpression of murine OSM in lungs of C57BL/6 mice using an adenovirus vector encoding murine OSM resulted in a vigorous inflammatory response by day 7 after intranasal administration, including marked extracellular matrix accumulation and eosinophil infiltration. Elevated levels of eotaxin mRNA in whole lung were detected at days 4 and 5. These data strongly support a role of OSM in lung inflammatory responses that involve eosinophil infiltration.
Langdon
Carrie
C
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
Kerr
Christine
C
Tong
Li
L
Richards
Carl D
CD
D016475:3T3 Cells; D000818:Animals; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000096:biosynthesis*; D004306:Dose-Response Relationship, Immunologic; D004804:Eosinophils / Q000276:immunology* / Q000473:pathology*; D005260:Female; D005347:Fibroblasts / Q000276:immunology* / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D053683:Oncostatin M; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D011657:Pulmonary Eosinophilia / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018121:Receptors, Cytokine / Q000502:physiology; D053677:Receptors, Oncostatin M; D015398:Signal Transduction / Q000276:immunology
C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D018836:Inflammation Mediators; C508352:Osm protein, mouse; D010455:Peptides; D018121:Receptors, Cytokine; D053677:Receptors, Oncostatin M; D053683:Oncostatin M