Hepatic fibrosis and gene expression changes induced by praziquantel treatment during immune modulation of Schistosoma japonicum infection.
In the present study fibrogenic gene expression was determined in murine Schistosoma japonicum infection during the progression of immune modulation of infection and following chemotherapy during the course of immune modulation. Histomorphometric analysis of granuloma size and collagen deposition revealed peak granuloma size in acute infection (5 weeks) and peak hepatic collagen content at 16 weeks of infection. Peak Type I collagen gene expression was concomitant with TGF-beta 1 gene expression at 8-11 weeks. Chemotherapy during either acute (9 weeks) or chronic (24, 28 weeks) infection resulted in increased collagen deposition and increased gene expression of Type I collagen and TGF-beta 1. However, chemotherapy at 14-16 weeks resulted in decreased levels of TGF-beta 1 gene expression and essentially minimal change in Type I collagen deposition and gene expression. These data indicate that chemotherapy of schistosomiasis japonica does not reverse hepatic fibrogenesis when administered in acute infection-when granuloma size is maximal-or in chronic infection. However, a beneficial effect on hepatic fibrogenesis is seen when chemotherapy is administered at 14-16 weeks post-infection, a time of decreasing granuloma size and maximal hepatic collagen content. Thus the ability to reverse schistosomal-induced hepatic fibrogenesis by chemotherapy may depend on disease stage.
Kresina
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Department of Medicine, Miriam Hospital, Brown University International Health Institute, Providence, RI 02906.
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D000818:Animals; D010478:Chemotherapy, Cancer, Regional Perfusion; D002908:Chronic Disease; D003094:Collagen / Q000096:biosynthesis; D005109:Extracellular Matrix / Q000378:metabolism*; D015870:Gene Expression; D006099:Granuloma; D008099:Liver / Q000737:chemistry; D008106:Liver Cirrhosis, Experimental / Q000209:etiology / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011223:Praziquantel / Q000494:pharmacology*; D012313:RNA / Q000032:analysis; D012554:Schistosomiasis japonica / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis
D016212:Transforming Growth Factor beta; D012313:RNA; D011223:Praziquantel; D003094:Collagen