THE EFFECT OF INTERFERON ALPHA(2B) ON THE EXPRESSION OF CYTOSKELETAL PROTEINS IN AN IN-VITRO MODEL OF WOUND CONTRACTION

Wound contraction is an essential component of wound healing, However, the development of scar contractures in tissues and organs disrupts n ormal organ integrity and produces functional deformities, Although in terferons alpha and gamma inhibit extracellular matrix protein product ion by fibroblasts, their effects on cytoskeletal protein mediated-wou nd contraction are as yet unclear, The fibroblast-populated collagen l attice is an in vitro assay that simulates wound contraction, When mat ched pairs of human hypertrophic scar and normal dermal fibroblast cul tures established from patients recovering from a thermal injury were used, interferon-alpha(2b) exposure before lattice formation was found to significantly inhibit contraction in a treatment time-dependent ma nner (p < 0.05). Fibroblasts generated contractile forces that were tr iphasic and serum sensitive (p < 0.01), Comparison of hypertrophic sca r and normal dermal fibroblasts revealed no significant differences in ability to induce lattice contraction, Northern blot analysis of mRNA s for the intracellular contractile proteins revealed that interferon- alpha(2b) significantly down-regulated mRNA levels of the actin isofor ms beta and gamma (50% to 60%) but had no significant effect on alpha- tubulin, vimentin, and alpha-actinin. Fibroblast-populated collagen la ttices were stained with rhodamine-labeled phalloidin to reveal filame ntous actin proteins, Marked morphologic alterations of the stress fib ers were associated with reductions in lattice contraction after inter feron-alpha(2b) treatment, Thus interferon-alpha(2b)'s inhibition of w ound contraction in vitro is associated with reductions in mRNA for be ta and gamma actin and distinct morphologic alterations in fibroblast stress fiber morphology.