The healing potential of wild type and recombinant S100A8 to attenuate skin wound inflammation

Abstract

BackgroundWounds represent a major health burden in our society and poorly healing wounds are a significant clinical problem worldwide, During the acute inflammatory, neutrophils which are normal wound scavengers seems to create additional tissue destruction and promote scar formation. This project examined the utility of using pluronic gel to deliver ala42S100A8, a peptide that repels neutrophils, to wounds, allowing more regenerative repair. MethodExcisional wound models on female BALB/c mice were made and 4 treatments including pluronic gel only group, Wild type S100A8 (1, 2, and 4g) with Pluronic gel, and ala42S100A8 (1, 2, and 4g) with Pluronic gel were applied to the wounds. Wounds were harvested at day 1 and day 3. Myeloperoxidase (MPO) protein level was examined using an ELISA kit and cytokine protein expression of CXCL1 (GRO-1), CXCL2 (MIP-2). IL-6, and TNF- was determined using a multiplex ELISA kit. ResultsMPO level in Pluronic gel treated wounds at day 1 was significantly higher than that in control, suggesting that the Pluronic gel itself causes increased inflammation in wounds, while treatment with 1g of s100A8 or 1 and 4g of ala42S100A8 seemed to decrease MPO at day 1 compared to the Pluronic gel treated wounds. Treatment with 1g of s100A8 also led to a decrease IL-6 and TNF- production at day 1 when compared to the Pluronic gel group, although no statistical difference was observed ConclusionsOur findings strongly suggest that wound inflammation is reduced by treatment with 1ug of S100A8. As such, this study provides proof-of-principal for further investigations of S100A8/ala42S100A8 as a wound therapeutic. Additional studies with lower doses and increased sample size, along with the use of alternative delivery systems, will provide important information about the utility of this approach.