Differential expression of collagen, MMP, TIMP and fibrogenic-cytokine genes in the granulomatous colon ofSchistosoma mansoni-infected mice

Abstract

Schistosomiasis mansoni is a major helminthic disease of the tropics characterised by chronic hepatic and intestinal granulomatous inflammation and fibrosis. The fibrotic response is regulated by the amount of collagen deposited in the tissues and the degradation of that collagen by matrix metalloproteinases (MMP). In the murine model of the disease, although hepatic granuloma formation and the ensuing fibrosis have been thoroughly examined, there is a dearth of information on the intestinal fibrotic process. The expression of fibrosis-related genes in the colons of chronically infected mice has therefore been investigated. Compared with that seen in uninfected mice, the expression of the genes coding for collagen of types I, III and IV was upregulated. Similarly, the messages for MMP-2, MMP-3 and MMP-8 were elevated, indicating the potential for collagen degradation. The genes for two tissue inhibitors of metalloproteinases (TIMP), TIMP-1 and TIMP-4, were, however, expressed at higher levels than those coding for the MMP. As a corollary, expression of the genes coding for three fibrogenic cytokines, transforming growth factor-beta, tumour necrosis factor and interleukin-4, was elevated. These data indicate that an imbalance in MMP:TIMP expression and enhanced levels of the messages for fibrogenic cytokines underlie the mechanism(s) of the colonic fibrosis seen in mice chronically infected with Schistosoma mansoni.