Topical nicotinic receptor activation improves wound bacterial infection outcomes and TLR2-mediated inflammation in diabetic mouse wounds. Journal Article

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Authors: Kishibe, M; Griffin, TM; Goslawski, M; Sinacore, J; Kristian, SA; Radek, KA
Article Title: Topical nicotinic receptor activation improves wound bacterial infection outcomes and TLR2-mediated inflammation in diabetic mouse wounds.
Abstract: The cholinergic anti-inflammatory pathway can directly affect skin antibacterial responses via nicotinic acetylcholine receptors (nAChRs). In particular, a7 nAChR (CHRNA7) present in the epidermis modulates the host response to wounding and/or wound bacterial infection. While physiologic inflammation is required to initiate normal wound repair and can be triggered by Toll-like receptor (TLR) activation, chronic inflammation is frequently observed in diabetic wounds, and can occur, in part, via excessive TLR2 activation or production. Consequently, this can delay physiologic wound healing responses and increase diabetic host susceptibility to bacterial infection. In this study, we demonstrate that topical nAChR activation diminishes bacterial survival and systemic dissemination in a mouse model of diabetic wound infection, while reducing wound TLR2 production, relative to control mice. We further determined that the AMP activity of diabetic mouse wounds is increased compared to control mice, but this effect is lost following topical nAChR activation. Finally, we observed that human diabetic wounds exhibit impaired a7 nAChR (CHRNA7) abundance and localization relative to human control (non-diabetic) skin. These findings suggest that topical administration of nAChR agonists may improve wound healing and infection outcomes in diabetic wounds by dampening TLR2-mediated inflammation and AMP response, and that the diabetic microenvironment may promote aberrant CHRNA7 production/activation that likely contributes to diabetic wound pathogenesis. This article is protected by copyright. All rights reserved.
Journal Title: Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society
ISSN: 1524-475X; 1067-1927
Publisher: Unknown  
Date Published: 2018