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/microg 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/microg 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.
Radek
Katherine A
KA
Alcohol Research Program, Burn and Shock Trauma Institute, Loyola University Medical Center, Maywood, Illinois, USA.
Kovacs
Elizabeth J
EJ
DiPietro
Luisa A
LA
D000435:Alcoholic Intoxication / Q000503:physiopathology*; D000818:Animals; D003094:Collagen / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D015849:Plasminogen Inactivators / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*
D015849:Plasminogen Inactivators; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D053773:Transforming Growth Factor beta1; D003094:Collagen; D014568:Urokinase-Type Plasminogen Activator; D020782:Matrix Metalloproteinases