Biol Res Nurs. 2010 Apr;11(4):336-44. doi: 10.1177/1099800409346333. Epub 2009 Dec 22.
The role of doxycycline as a matrix metalloproteinase inhibitor for the treatment of chronic wounds.
Abstract
Many
chronic wounds fail to heal with conventional therapy, resulting in
disability and impaired quality of life. New technologies using
recombinant growth factors, autologous growth factors, or bioengineered
skin-tissue substitutes have been shown to be effective, but these
treatments are costly. An effective, low-cost treatment to improve
healing of chronic wounds is needed. The molecular environment of
chronic wounds, like many other chronic inflammatory diseases, contains
abnormally high levels of proinflammatory cytokines (tumor necrosis
factor [TNF]-alpha and interleukin [IL]-1beta]) and matrix
metalloproteinases (MMPs), which impair normal wound healing. In animal
models and clinical studies of ulcerative diseases, doxycycline, an
inexpensive and Food and Drug Administration (FDA)-approved antibiotic,
appears to inhibit members of the MMP superfamily like MMPs and
TNF-alpha-converting enzyme (TACE). This article provides an overview of
the roles of MMPs and intrinsic tissue inhibitors of metalloproteinases
(TIMPs) in wound healing and the damaging effects of chronically
elevated levels of MMPSs in chronic wounds. It also explores the use of
topical doxycycline, a synthetic MMP inhibitor (MMPI), to enhance
healing of chronic wounds.
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