Effect of colchicine on collagen synthesis by liver fibroblasts in murine schistosomiasis.

ABSTRACT

Colchicine, an antimicrotubular agent, was shown to block the transcellular movement of certain structural macromolecules such as collagen. In the present study, the effect of colchicine on collagen synthesis and secretion by monolayer cultures of fibroblasts from livers of mice infected with Schistosoma mansoni was investigated. The effect of colchicine on proliferation of these fibroblasts was studied as well. Collagen and non-collagen protein synthesis was measured by incubating cultures with [14C]proline and measuring the incorporation of radioactivity into these protein fractions in both culture media and cell layers. Proliferation was measured by [3H]thymidine uptake. The isolated fibroblasts actively formed collagen and secreted most of it into the culture medium; 10-20% of the collagenase-sensitive radioactive protein remained in the cell layer. The addition of colchicine to culture medium led to selective inhibition of collagen formation with negligible effects on non-collagen protein synthesis. Fibroblast proliferation was also reduced by colchicine treatment. Both inhibition of collagen synthesis and inhibition of fibroblast proliferation were dose-dependent. Comparison of medium and cell layer collagen radioactivity confirmed inhibition of synthesis rather than only inhibition of secretion. These data suggest that colchicine has a specific effect on synthesis of collagen and proliferative activity by fibroblasts from S. mansoni-infected liver and may, therefore, be useful in modulating schistosomal hepatic fibrosis.