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Adenovirus vector expressing mouse oncostatin M induces acute-phase proteins and TIMP-1 expression in vivo in mice
1Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
Abstract:
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.
Insights
Mouse oncostatin M (MuOSM) delivered via adenovirus (AdMuOSM) effectively boosts acute-phase proteins and tissue inhibitor of metalloproteinases-1 (TIMP-1) in vivo. This study demonstrates AdMuOSM
Area of Science:
- Biotechnology
- Immunology
- Molecular Biology
Background:
- Mouse oncostatin M (MuOSM) is known to regulate acute-phase protein production in hepatocytes and tissue inhibitor of metalloproteinases-1 (TIMP-1) in fibroblasts in vitro.
- Adenovirus (Ad) vectors are commonly used for gene delivery in preclinical studies.
Purpose of the Study:
- To investigate the in vivo effects of recombinant adenovirus encoding mouse oncostatin M (AdMuOSM) on acute-phase protein and TIMP-1 expression.
- To assess both local and systemic responses following AdMuOSM administration in mice.
Main Methods:
- Generation of an adenovirus encoding MuOSM (AdMuOSM).
- Administration of AdMuOSM via intramuscular, intratracheal, and intraperitoneal routes in mice.
- Measurement of serum cytokine and acute-phase protein levels (IL-6, SAP, AGP).
- Assessment of TIMP-1 mRNA levels in lung tissue using Northern blots.
Main Results:
- Intramuscular AdMuOSM injection induced significant increases in serum IL-6, SAP, and AGP levels, peaking at day 3 and returning to baseline by day 7.
- Intratracheal AdMuOSM administration elevated TIMP-1 mRNA levels in the lungs, correlating with transgene expression.
- Intraperitoneal AdMuOSM also led to increased TIMP-1 mRNA in lung tissue.
Conclusions:
- Recombinant AdMuOSM effectively induces systemic acute-phase responses and local TIMP-1 expression in vivo.
- The findings support the in vitro observations of OSM's role in regulating acute-phase proteins and TIMP-1.
- AdMuOSM demonstrates potential for modulating inflammatory and tissue remodeling processes in vivo.