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Abstract
Background. Glucocorticoids impair wound healing and cause surgical morbidity. Heat shock proteins
are essential to cellular stress tolerance and arc associated with glucocorticoids.
The adrenal heat shock protein response is under hypothalmic-pituitary-adrenal-axis
control, whereas the vascular response is associated with a-1 receptors. Because heat
shock proteins affect cellular stress responses and are under hypothalmic-pituitary-adrenal-axis
control in other tissues, use postulated an association between heat shock proteins
and glucocorticoids in healing wounds.
Methods.Modified Hunt-Schilling wound chambers were implanted subcutaneously in rats. They
received subcutaneous time-release dexamethasone (25 mg) or placebo pellets. Wound
chamber heat shock protein 25 and heat shock protein 72/73 were serially assayed for
21 days with western analysis and immunocytochemistry.
Results. Dexamethasone caused Cushing's syndrome with ∼ 70% weekly weight-loss and adrenal
atrophy. Total wound tissue decreased 90% with profound differences in molecular wound
responses manifested by decreased heat shock protein 25, 72, and 73 in animals treated
with dexamethasone despite equal protein loads. Furthermore dexamethasone caused heat
shock protein 72 redistribution by immunocytochemistry.
Conclusions. This study represents the first description of heat shock proteins in a wound healing
model and demonstrates tissue-specific decrease of heat shock proteins with glucocorticoid
therapy. Thus the heat shock protein response is intimately associated with. normal
wound healing and is profoundly altered in subjects with Cushing's syndrome. Manipulation
of this response may have clinical importance in wound healing.
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Article info
Footnotes
☆Supported in part by the George H.A. Clowes, Jr. Memorial Research Award of the American College of Surgeons and an award from the National Institutes of Health (NIDDK, DK 02064-01).
☆☆Presented at the Fifteenth Annual Meeting of the American Association of Endocrine Surgeons, Dearborn, Mich., April 17–19, 1994.
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Copyright
© 1994 Published by Elsevier Inc.
