Adenoviral transfer of the murine oncostatin M gene suppresses dextran-sodium sulfate-induced colitis.
The use of biologics has promising potential in the treatment of inflammation. Studies with cultured cells and mouse models of disease have ascribed proinflammatory and anti-inflammatory functions to oncostatin M (OSM) and the related cytokine, interleukin-6 (IL-6). Here, we examined the effect of systemic administration of adenoviral (Ad) vectors encoding either murine OSM (AdMuOSM) or murine IL-6 (AdMuIL-6) in a mouse model of colitis. BALB/c mice were treated with a 5-day course of 4% dextran-sodium sulfate (DSS) water with or without administration of adenoviral vectors (i.p. or i.m. at 10(7) plaque-forming units [pfu]) given as a cotreatment or therapy. The deletion variant of the adenovirus served as a control for adenoviral infection. Colitis was assessed by (1) morphology (damage score, macrophage infiltration, apoptosis) and (2) function (myeloperoxidase activity and Ussing chamber analysis of epithelial ion transport). Infection with adenovirus alone did not affect colonic form or function. AdMuOSM (either i.p. or i.m.) significantly reduced the severity of the DSS-induced colitis. There was less damage, reduced macrophage infiltration, fewer apoptotic bodies, and a significant improvement in stimulated ion transport in colonic tissues from the treated mice. No benefit of AdMuIL-6 treatment was observed in this model system. Thus, systemic administration of AdMuOSM given as a cotreatment and to a lesser extent as a therapy was found to be of benefit in DSS-induced colitis, a murine model of inflammatory bowel disease (IBD).
Sanchez
Ana L
AL
Intestinal Disease Research Programme, McMaster University, Hamilton, Ontario, Canada.
Langdon
Carrie M
CM
Akhtar
Mahmood
M
Lu
Jun
J
Richards
Carl D
CD
Bercik
Premysl
P
McKay
Derek M
DM
D000209:Acute-Phase Proteins / Q000378:metabolism; D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D003092:Colitis / Q000139:chemically induced* / Q000517:prevention & control*; D003106:Colon / Q000187:drug effects / Q000473:pathology; D016264:Dextran Sulfate / Q000037:antagonists & inhibitors / Q000633:toxicity*; D005822:Genetic Vectors; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D053683:Oncostatin M; D010455:Peptides / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection / Q000379:methods
D000209:Acute-Phase Proteins; C508351:OSM protein, human; C508352:Osm protein, mouse; D010455:Peptides; D011994:Recombinant Proteins; D053683:Oncostatin M; D016264:Dextran Sulfate