Androstenediol reduces the anti-inflammatory effects of restraint stress during wound healing.
Restraint stress (RST) delays wound closure and suppresses pro-inflammatory gene expression by a glucocorticoid-dependent mechanism. Because androstenediol (AED) ameliorates many of the anti-inflammatory influences of glucocorticoids (GC) in vitro, it was hypothesized that treatment of stressed animals with AED would ameliorate the suppressive influence of restraint and restore healing to control levels. To test this hypothesis, male CD1 mice were subjected to nightly cycles of RST beginning 3 days prior to placement of two 3.5 mm full-thickness cutaneous wounds. To assess the influence of AED treatment on wound repair, mice were injected subcutaneously with 2.0 mg of AED or an equivalent volume of delivery vehicle (VEH) prior to wounding. The rate of wound closure was assessed daily by photoplanimetry. In addition, at 3, 6, 12, and 24 h post wounding, IL-1beta, MCP-1, and PDGF RNAs were quantified in wounds as a measure of inflammatory gene expression. The data showed that RST significantly delayed closure as compared to controls. In parallel, RST significantly decreased IL-1beta and PDGF gene expression as early as 12 h after wounding. In contrast, treatment with AED prevented the stress-induced delay in healing. Whereas wounds on VEH/RST mice did not achieve 50% closure until day 7, wounds on AED-treated animals, whether subjected to RST or not, had closed by 50% within 3 days of wounding. In addition, AED treatment prevented the stress-induced suppression of IL-1beta and PDGF gene expression 24 h after injury. Therefore, AED may provide a pharmacologic approach to ameliorate the anti-inflammatory effects of behavioral stress and in doing so, may improve tissue repair.
Head
Cynthia C
CC
Section of Oral Biology, College of Dentistry, The Ohio State University, Columbus, OH 43218, USA.
Farrow
Michael J
MJ
Sheridan
John F
JF
Padgett
David A
DA
D015114:Androstenediol / Q000276:immunology*; D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism; D012313:RNA / Q000032:analysis; D012149:Restraint, Physical / Q000502:physiology; D012867:Skin / Q000276:immunology* / Q000293:injuries / Q000378:metabolism; D014945:Wound Healing / Q000276:immunology* / Q000502:physiology
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D053583:Interleukin-1beta; D010982:Platelet-Derived Growth Factor; D012313:RNA; D015114:Androstenediol