Gamma-interferon treatment inhibits collagen deposition in murine schistosomiasis.
Since interferons have been shown to affect the synthesis of matrix proteins such as collagen in several in vitro systems, the potential role of gamma-interferon in inhibiting hepatic fibrosis was investigated. Hepatic cells, consisting primarily of hepatocytes, were treated with recombinant gamma-interferon for 24 hr. Northern blot hybridization showed that gamma-interferon treatment caused a profound decrease in pro-alpha 2(I)collagen mRNA levels but an increase in beta-actin mRNA content. The effects of gamma-interferon were then studied in an in vivo model of hepatic fibrogenesis, murine schistosomiasis. Schistosoma-infected mice were treated with daily i.m. injections of gamma-interferon for a 4-week period starting 4 weeks after the initial infection. gamma-Interferon treatment decreased collagen deposition as determined by histologic evaluation and measurement of total liver collagen content. Northern blots showed Types I and III procollagen mRNA levels for treated, infected animals to be only 32 and 29% that of infected controls, but beta-actin mRNA levels were significantly elevated. These results indicate a potential role for gamma-interferon as an antifibrogenic agent in vivo.
Czaja
M J
MJ
Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461.
Weiner
F R
FR
Takahashi
S
S
Giambrone
M A
MA
van der Meide
P H
PH
Schellekens
H
H
Biempica
L
L
Zern
M A
MA
D000199:Actins / Q000096:biosynthesis; D000818:Animals; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D004195:Disease Models, Animal; D005260:Female; D007371:Interferon-gamma / Q000627:therapeutic use*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000469:parasitology; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011347:Procollagen / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins; D012555:Schistosomiasis mansoni / Q000150:complications / Q000188:drug therapy / Q000378:metabolism* / Q000469:parasitology
D000199:Actins; D011347:Procollagen; D011994:Recombinant Proteins; D007371:Interferon-gamma; D003094:Collagen