Adenovirus Vector Expressing Mouse Oncostatin M Induces Acute-Phase Proteins and TIMP-1 Expression In Vivo in Mice

Mouse oncostatin M (MuOSM) regulates the production of acute-phase proteins by hepatocytes as well as tissue inhibitor of metalloproteinases-1 (TIMP-1) production by fibroblasts in vitro. We have generated an adenovirus (Ad) encoding MuOSM and tested the effects of administration of recombinant AdMuOSM to mice in vivo. On intramuscular injection, AdMuOSM (5 X 10(7) plaque-forming units, pfu) induced an increase in serum levels of interleukin-6 (IL-6) as well as the acute-phase proteins serum amyloid A (SAP) and alpha1-acid glycoprotein (AGP) at day 1. SAP and AGP concentrations were elevated to greater levels at day 3 and decreased to near control levels at day 7. Intratracheal treatment with AdMuOSM induced TIMP-1 mRNA levels (as assessed by Northern blots) that corresponded to the presence of transgene MuOSM mRNA levels. TIMP-1 was elevated at day 1 and day 3 and less consistently at day 7 after administration. Intraperitoneal treatment with AdMuOSM also resulted in elevation of TIMP-1 mRNA in lung tissue. These results show that AdMuOSM can induce both local and systemic effects and demonstrate in vivo effects of OSM that are consistent with in vitro studies on acute-phase protein and TIMP-1 expression.