title: Ala42S100A8 ameliorates psychological-stress impaired cutaneous wound healing.
abstract: Although wound healing is generally a successful, carefully orchestrated and evolutionary sound process, it can be disregulated by extrinsic factors such as psychological-stress. In the SKH-1 restraint stress model of cutaneous wound healing, the rate of wound closure is approximately 30% slower in stressed mice. Delay in healing is associated with exaggerated acute inflammation and deficient bacterial clearance at the wound site. It has been suggested that wound hypoxia may contribute to the mechanisms of impaired cutaneous wound healing in the mouse SKH-1 model. Optimal healing of a cutaneous wound is a stepwise repair program. In its early phase, an inflammatory oxidative burst generated by neutrophils is observed. About 40% of neutrophils cytosolic protein weight is comprised of two calcium binding proteins S100A8 and S100A9. Our previous work has shown that S100A8 act as an oxidation-sensitive repellent of human neutrophils in-vitro. Ala(42)S100A8, a site-directed mutant protein is resistant to oxidative inhibition and inhibits neutrophil recruitment in-vivo. Accordingly, we tested the hypothesis that S100A8 may ameliorate wound healing in this model. We examined the effect of wild-type and ala(42)S100A8 for their ability to ameliorate wound closure rates. The data indicated that a single local application of ala(42)S100A8 ameliorated the decreased rate of wound closure resulting from stress. This occurred without significantly affecting wound bacterial clearance. Wild-type S100A8 only had a partial beneficial effect on the rate of wound closure. Those findings support further translational studies of S100 based intervention to ameliorate impaired wound healing.
authors.affiliation: Department of Oral Medicine and Diagnostic Sciences, College of Dentistry, University of Illinois at Chicago, 801 S. Paulina St., Chicago, IL 60612-7213, USA. sroussih@uic.edu
authors.forename: Herve Y
authors.initials: HY
authors.lastname: Sroussi
authors.forename: Richard L
authors.initials: RL
authors.lastname: Williams
authors.forename: Qing L
authors.initials: QL
authors.lastname: Zhang
authors.forename: Dana
authors.initials: D
authors.lastname: Villines
authors.forename: Phillip T
authors.initials: PT
authors.lastname: Marucha