Selective inhibition of human diploid fibroblast collagen synthesis by interferons.

Abstract

Abstract. The effects of a-and -interferons (IFNs) on collagen production by confluent human diploid fibroblasts in culture were examined. It was found that partially purified a-IFNs and affinity purified -y-IFNs caused >50% inhibition of collagen synthesis by these cells independently of their effect on cell proliferation. Recombinant a-IFNs showed a similar effect (38.8% inhibition), indicating that collagen synthesis inhibition was a constitutive property of IFNs. Collagen synthesis inhibition by IFNs was concentration dependent. Gel filtration chromatography of the newly synthesized proteins from the media of fibroblasts incubated with partially purified a-IFNs demonstrated a selective depression of molecules eluting in the region of procollagen. No detectable increase in collagen degradation products or underhydroxylation of procollagen was observed. Short-term kinetic studies further demonstrated that the major effect of IFNs was due to a net decrease in fibroblast collagen production rather than to impairment of secretion or increased extracellular degradation of the newly synthesized molecules. These results indicate that a-and -y-IFNs are potent inhibitors of human fibroblast collagen production and suggest that they may play an important role in the regulation of normal and pathologic fibrogenesis.

Baculovirus-mediated interferon alleviates dimethylnitrosamine-induced liver cirrhosis symptoms in a murine model

“…[32][33][34][35] In vivo models of enhanced collagen synthesis have also revealed that IFN-g reduces the collagen accumulation associated with foreign bodies, skin wound healing and bleomycin-induced lung AcMNPV-mediated IFN alleviates LC in a murine model Y Nishibe et al fibrosis. [36][37][38] Further, in liver fibrosis induced by Schistosoma mansoni infection, IFN-g significantly reduces collagen accumulation, and type I and III procollagen mRNA levels.…”

Echinococcus multilocularisinfection in mice:in vivotreatment with a low dose of IFN-γ decreases metacestode growth and liver fibrogenesis

“…IFN-γ is a major mediator of resistance against a wide range of pathogens through macrophage activation (reviewed by Murray, 1988). On the other hand, IFN-γ in vitro inhibits the synthesis of type I collagen by human fibroblasts (Jimenez et al, 1984) and by human myofibroblastc Ito cells (Mallat et al, 1995). Moreover, an in vivo treatment with IFN-γ decreases collagen deposition and types I and III procollagen mRNA levels in the liver of S.mansoni-infected mice (Czaja et al, 1989).…”

The effects of 5-fluorouracil and interferon-α on early healing of experimental intestinal anastomoses

“…Alternatively, it could be that interferon-x has less effect on matrix production than the other interferons. Experiments with isolated cells show this to be true for fibroblast collagen synthesis, both on the protein (Jimenez et al, 1984;Duncan and Berman. 1985) and the mRNA level (Duncan et al.…”