Role of the snake venom toxin jararhagin in proinflammatory pathogenesis: in vitro and in vivo gene expression analysis of the effects of the toxin.

To assess the indirect effects of snake venom metalloproteinases (SVMP) on host tissue local necrosis, we investigated the effect of the SVMP jararhagin on the gene expression profiles of human fibroblasts in vitro and mouse tissue in vivo. Two functional classes of up-regulated proteins, cell death and inflammatory disease were identified as being significantly populated. The changes in gene expression observed by qRT-PCR on laser microdissected mouse muscle tissue treated with jararhagin were similar with significant up-regulation of proinflammatory transcripts such as IL-1 beta, IL-6, CXCL1, CXCL2, IL-8, and apoptosis, inflammation responsive transcripts such as TNF-alpha induced protein 6. Proteolytically inactive jararhagin had no effect on the gene expression profile of fibroblasts, indicating proteolysis as the primary mechanism affecting gene expression of cells and tissues resulting in a proinflammatory, pro-apoptotic host response which likely exacerbates the local necrosis frequently observed at the site of envenoming.