Oncostatin M is a proinflammatory mediator. In vivo effects correlate with endothelial cell expression of inflammatory cytokines and adhesion molecules.
Oncostatin M is a member of the IL-6 family of cytokines that is primarily known for its effects on cell growth. Endothelial cells have an abundance of receptors for oncostatin M, and may be its primary target. We determined if oncostatin M induces a key endothelial cell function, initiation of the inflammatory response. We found that subcutaneous injection of oncostatin M in mice caused an acute inflammatory reaction. Oncostatin M in vitro stimulated: (a) polymorphonuclear leukocyte (PMN) transmigration through confluent monolayers of primary human endothelial cells; (b) biphasic PMN adhesion through rapid P-selectin expression, and delayed adhesion mediated by E-selectin synthesis; (c) intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 accumulation; and (d) the expression of PMN activators IL-6, epithelial neutrophil activating peptide-78, growth-related cytokine alpha and growth-related cytokine beta without concomitant IL-8 synthesis. The nature of the response to oncostatin M varied with concentration, suggesting high and low affinity oncostatin M receptors independently stimulated specific responses. Immunohistochemistry showed that macrophage-like cells infiltrating human aortic aneurysms expressed oncostatin M, so it is present during a chronic inflammatory reaction. Therefore, oncostatin M, but not other IL-6 family members, fulfills Koch's postulates as an inflammatory mediator. Since its effects on endothelial cells differ significantly from established mediators like TNFalpha, it may uniquely contribute to the inflammatory cycle.
Modur
V
V
Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA.
Feldhaus
M J
MJ
Weyrich
A S
AS
Jicha
D L
DL
Prescott
S M
SM
Zimmerman
G A
GA
McIntyre
T M
TM
D000818:Animals; D001011:Aorta / Q000276:immunology / Q000473:pathology; D001014:Aortic Aneurysm / Q000276:immunology* / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis* / Q000494:pharmacology; D019040:E-Selectin / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D006801:Humans; D007249:Inflammation; D007279:Injections, Subcutaneous; D015850:Interleukin-6 / Q000096:biosynthesis; D051379:Mice; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D053683:Oncostatin M; D019007:P-Selectin / Q000502:physiology; D010452:Peptide Biosynthesis; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins
D015815:Cell Adhesion Molecules; D016207:Cytokines; D019040:E-Selectin; D015850:Interleukin-6; C508351:OSM protein, human; C508352:Osm protein, mouse; D019007:P-Selectin; D010455:Peptides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D053683:Oncostatin M