The aim of the current study was to investigate the effect of nicotine in an experimental mouse model of cutaneous injury and healing responses, during the inflammatory phase of repair. Nicotine injection in full-thickness excisional skin wounds minimally affected inflammatory mediators like TNF, IL-6 and IL-12 while it induced a down-regulation in the expression of growth factors like VEGF, PDGF, TGF-β1 and TGF-β2, and the anti-inflammatory cytokine IL-10. Analysis of wound closure rate indicated no significant differences between nicotine and saline injected controls. In-vitro studies using bone marrow derived macrophages, resident peritoneal macrophages and RAW 264.7 macrophages, indicated that nicotine down-regulates TNF production. Moreover, nicotine was shown to down-regulate VEGF, PDGF and TGF-β1 in both bone marrow derived macrophages and RAW 264.7 cells. Using an NF-κB luciferase reporter RAW 264.7 cell line, we show that nicotine effects are minimally dependent on NF-κB inhibition. Moreover, nicotinic acetylcholine receptor (nAChR) subunit expression analyses indicated that while β2 nAChR subunit is expressed in mouse macrophages, α7 nAChR is not. In conclusion, while skin inflammatory parameters were not significantly affected by nicotine, a down-regulation of growth factor expression in both mouse skin and macrophages was observed. Reduced growth factor expression by nicotine might contribute, at least in part, to the overall detrimental effects of tobacco use in wound healing and skin diseases.
Keywords: Cytokines; Growth factors; IL-12; IL-6; Inflammation; Macrophages; Nicotine; PDGF; TGF-β1; TGF-β2; TNF; VEGF; Wound repair; interleukin 12; interleukin 6; platelet derived growth factor; transforming growth factor beta 1; transforming growth factor beta 2; tumor necrosis factor; vascular endothelial growth factor.
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