Matrix proteolytic activity during wound healing: Modulation by acute ethanol exposure

Background: Clinical studies demonstrate that intoxicated patients exhibit an increased incidence of wound healing complications. Previous studies in a murine excisional wound model revealed that acute ethanol exposure impairs the wound healing response, causing decreased angiogenesis and a significant reduction in wound collagen content. Methods: Using the same murine model of excisional wounding, we examined the effect of a single dose of ethanol on the overall collagen content and collagen type I and type III mRNA expression, transforming growth factor-beta (TGF-beta) production, and levels of several components of the extracellular matrix proteolytic cascade. Results: Wounds from ethanol-treated mice exhibited a significant decrease in collagen and in the production of collagen type I mRNA compared with saline controls. Exposure to ethanol also caused significant increase in wound TGF-beta by day 2 after injury (1.69 +/- 0.29 vs 12.34 +/- 3.97 pg/mu g protein, p < 0.01). In addition, wounds from mice exposed to ethanol had significantly increased levels of active urokinase plasminogen activator at day 7, (205.10 +/- 48.79 vs 642.70 +/- 159.80 pg/mu g protein, p < 0.001). The level of matrix metalloproteinase-8, a collagen type I proteinase, was 2.2-fold higher in wounds of ethanol-treated mice compared with control at day 7 (p < 0.05). Conclusions: These studies demonstrate that a single dose of ethanol decreases collagen production, increases the production of TGF-beta and increases levels of matrix degrading enzymes. This alteration in protease balance may partially explain the impaired wound healing that follows acute alcohol intoxication.