Oncostatin M stimulates proliferation, induces collagen production and inhibits apoptosis of human lung fibroblasts.
1. Oncostatin M (OSM), a member of the interleukin-6 (IL-6) cytokine family, acts on a variety of cells and elicits diversified biological responses, suggesting potential roles in the regulation of cell survival, differentiation and proliferation. 2. We have examined the effect of OSM on the regulation of human lung fibroblast proliferation, collagen production and spontaneous apoptosis. The proliferative effects of OSM (0.5 - 100 ng ml(-1)) were assessed using a MTS assay as well as [(3)H]-thymidine incorporation and cell counts at 24 and 48 h. Hydroxyproline was measured as an index of procollagen production by high pressure liquid chromotography (HPLC). Apoptosis was determined by annexin staining. 3. OSM enhanced the mitotic activity of lung fibroblasts in a time and dose dependent manner. Maximum proliferation of 57% above control was observed after incubation for 48 h with 2 ng ml(-1) OSM (P<0.05). 4. Incubation with the mitogen activated protein kinase (MAPK) kinase inhibitor, PD98059 or the tyrosine kinase inhibitor, genestein both significantly reduced the mitogenic effect of OSM (P<0.05). 5. In contrast, proliferation in response to OSM was not regulated by induction of cyclo-oxygenase and subsequent prostaglandin E(2) (PGE(2)) release or by IL-6. 6. OSM also stimulated fibroblasts to synthesize pro-collagen by a maximum of 35% above control levels after 48 h (P<0.05). 7. OSM significantly inhibited the spontaneous apoptosis of fibroblasts at 24 and 48 h. 8. These results provide evidence that OSM has pro-fibrotic properties and suggest that it may play a role in normal lung wound repair and fibrosis.
Scaffidi
Amelia K
AK
Asthma and Allergy Research Institute, Sir Charles Gairdner Hospital and Department of Medicine, University of Western Australia, Nedlands, Western Australia 6009.
Mutsaers
Steven E
SE
Moodley
Yuben P
YP
McAnulty
Robin J
RJ
Laurent
Geoffrey J
GJ
Thompson
Philip J
PJ
Knight
Darryl A
DA
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D003094:Collagen / Q000096:biosynthesis*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D053683:Oncostatin M; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats
C508351:OSM protein, human; D010455:Peptides; D053683:Oncostatin M; D003094:Collagen