Molecular and cellular basis of hepatic fibrogenesis in experimental schistosomiasis mansoni infection.
Morbidity in schistosomiasis mansoni occurs primarily as a result of the complications of hepatic fibrosis. Yet, the pathogenesis of schistosomal hepatic fibrosis is poorly understood. The fact that the hepatic egg granuloma is the hallmark of this infection suggests a potential role for granulomatous inflammation in hepatic fibrogenesis. Our studies in a murine schistosomiasis model indicate that hepatic granuloma cells secrete a variety of fibrogenic cytokines that may initiate the scarring process. Among these cytokines, we identified a novel protein that we designated fibroblast stimulating factor-1 (FsF-1). FsF-1 is a lymphokine that can stimulate fibroblast growth and matrix synthesis. A notable feature of hepatic fibrosis in this model is that production of FsF-1 and other granuloma-derived fibrogenic cytokines is down-regulated in chronic infection, an event that may be under immunological control. The spontaneous reduction of FsF-1 secretion presumably accounts for reduced scar formation late in infection of mice. In the context of relevant clinical studies, our findings engender the hypothesis that Symmer's fibrosis may develop in a small subpopulation of individuals as a result of immunogenetically-determined dysregulation of fibrogenic cytokine production.
Department of Medicine, New England Medical Center Hospitals, Boston, MA 02111.
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Wyler
D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D005347:Fibroblasts / Q000378:metabolism; D006099:Granuloma / Q000378:metabolism / Q000469:parasitology / Q000473:pathology*; D008103:Liver Cirrhosis / Q000378:metabolism / Q000469:parasitology / Q000473:pathology*; D008107:Liver Diseases / Q000378:metabolism / Q000469:parasitology / Q000473:pathology*; D008222:Lymphokines / Q000502:physiology*; D051379:Mice; D008954:Models, Biological; D010063:Ovum / Q000276:immunology; D012555:Schistosomiasis mansoni / Q000473:pathology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D016207:Cytokines; D008222:Lymphokines; C085978:fibroblast stimulating factor-1