Modulation of extracellular matrix using adenovirus vectors.
Metabolism of the extracellular matrix (ECM) is a complex process that becomes disregulated in disease states characterized by chronic inflammation of joints, as is seen in rheumatoid arthritis or fibrosis of the lung. The participation of certain cytokines in this process is generally accepted (transforming growth factor-beta induces fibrosis), while the roles of other cytokines are less clear. Oncostatin M (OSM) is a member of the interleukin-6/leukaemia inhibitory factor (or gp130) cytokine family, and its participation in inflammation and the regulation of ECM metabolism is supported by a number of activities identified in vitro, including regulation of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinases-1. Local overexpression of transforming growth factor-beta has been shown to be fibrogenic in mouse lung, whereas local OSM overexpression via intra-articular administration has been shown to induce a pannus-like inflammatory response in the synovium of mouse knee joints. Here we examine the effects of OSM in the context of those of transforming growth factor-beta using an established adenovirus vector that expresses mOSM (AdmOSM). We administered the virus intra-nasally into Balb/C mice to achieve high expression of OSM in the lung, and examined the effects at various time points. AdmOSM resulted in a vigorous inflammatory response by day 7 which was characterized by an elevation of neutrophil and mononuclear cell numbers and a marked increase in collagen deposition. These data support the use of such systems to study the ECM in vivo, and indicate a potential role for OSM in inflammatory responses that can modulate steady-state ECM deposition in Balb/C mice.
Richards
C D
CD
Centre for Gene Therapeutics, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada L8N 3Z5. richards@mcmaster.ca
Kerr
C
C
Tong
L
L
Langdon
C
C
D016475:3T3 Cells; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D016207:Cytokines / Q000494:pharmacology; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D005822:Genetic Vectors; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D053683:Oncostatin M; D010455:Peptides / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics
D016207:Cytokines; C508352:Osm protein, mouse; D010455:Peptides; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D053683:Oncostatin M