Keratinocyte nicotinic acetylcholine receptor activation modulates early TLR2-mediated wound healing responses Journal Article

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Authors: Kishibe, M; Griffin, T. M.; Radek, K. A.
Article Title: Keratinocyte nicotinic acetylcholine receptor activation modulates early TLR2-mediated wound healing responses
Abstract: The cholinergic anti-inflammatory pathway spans several macro- and micro-environments to control inflammation via alpha7 nicotinic acetylcholine receptors (nAChRs). Physiologic inflammation is necessary for normal wound repair and is triggered, in part, via Toll-like receptors (TLRs). Here, we demonstrate that keratinocyte nAChR activation dampens TLR2-mediated migration and pro-inflammatory cytokine and antimicrobial peptide (AMP) production, which is restored by a alpha7-selective nAChR antagonist. The mechanism of this response occurs by blocking the NF-kappaB and Erk1/2 pathway during early and late wound healing. In a mouse model of Staphylococcus aureus wound infection, topical nAChR activation reduces wound AMP and TLR2 production to augment bacterial survival in wild-type mice. These findings suggest that aberrant alpha7 nAChR activation may impair normal wound healing responses, and that pharmacologic administration of topical nAChR antagonists may improve wound healing outcomes in wounds necessitating a more robust inflammatory response.
Journal Title: International immunopharmacology
ISSN: 1878-1705; 1567-5769
Publisher: Elsevier Inc  
Date Published: 2015
Language: ENG
DOI/URL:

S1567-5769(15)00285-4
Notes: LR: 20150713; CI: Copyright (c) 2015; GR: R01 AR061497/AR/NIAMS NIH HHS/United States; JID: 100965259; OTO: NOTNLM; 2015/03/18 [received]; 2015/05/18 [revised]; 2015/05/29 [accepted]; aheadofprint