Burn Injury Alters Epidermal Cholinergic Mediators and Increases HMGB1 and Caspase 3 in Autologous Donor Skin and Burn Margin.

Journal Article (Journal Article)

Burn wound healing complications, such as graft failure or infection, are a major source of morbidity and mortality in burn patients. The mechanisms by which local burn injury alters epidermal barrier function in autologous donor skin and surrounding burn margin are largely undefined. We hypothesized that defects in the epidermal cholinergic system may impair epidermal barrier function and innate immune responses. The objective was to identify alterations in the epidermal cholinergic pathway, and their downstream targets, associated with inflammation and cell death. We established that protein levels, but not gene expression, of the α7 nicotinic acetylcholine receptor (CHRNA7) were significantly reduced in both donor and burn margin skin. Furthermore, the gene and protein levels of an endogenous allosteric modulator of CHRNA7, secreted mammalian Ly-6/ urokinase-type plasminogen activator receptor-related protein-1, and acetylcholine were significantly elevated in donor and burn margin skin. As downstream proteins of inflammatory and cell death targets of nAChR activation, we found significant elevations in epidermal High Mobility Group Box Protein 1 and caspase 3 in donor and burn margin skin. Lastly, we employed a novel in vitro keratinocyte burn model to establish that burn injury influences the gene expression of these cholinergic mediators and their downstream targets. These results indicate that defects in cholinergic mediators and inflammatory/apoptotic molecules in donor and burn margin skin may directly contribute to graft failure or infection in burn patients.

Full Text

Duke Authors

Cited Authors

  • Holmes, CJ; Plichta, JK; Gamelli, RL; Radek, KA

Published Date

  • February 2017

Published In

Volume / Issue

  • 47 / 2

Start / End Page

  • 175 - 183

PubMed ID

  • 27648692

Pubmed Central ID

  • PMC5235952

Electronic International Standard Serial Number (EISSN)

  • 1540-0514

Digital Object Identifier (DOI)

  • 10.1097/SHK.0000000000000752


  • eng

Conference Location

  • United States