title: Nicotine effect on inflammatory and growth factor responses in murine cutaneous wound healing.
abstract: 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.
authors.affiliation: Department of Plastic Surgery, Maastricht University Medical Center, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands; Department of Surgery, NUTRIM School for Nutrition, Toxicology & Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands. Electronic address: sofia.xanthoulea@maastrichtuniversity.nl.
authors.forename: Sofia
authors.initials: S
authors.lastname: Xanthoulea
authors.forename: An
authors.initials: A
authors.lastname: Deliaert
authors.forename: Andrea
authors.initials: A
authors.lastname: Romano
authors.forename: Sander S
authors.initials: SS
authors.lastname: Rensen
authors.forename: Wim A
authors.initials: WA
authors.lastname: Buurman
authors.forename: Rene' R W J
authors.initials: RR
authors.lastname: van der Hulst
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009538:Nicotine / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism; D012867:Skin / Q000293:injuries / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D053781:Transforming Growth Factor beta2 / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000378:metabolism
chemical_list: D016207:Cytokines; D009538:Nicotine; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D042461:Vascular Endothelial Growth Factor A; D064569:alpha7 Nicotinic Acetylcholine Receptor; C467480:vascular endothelial growth factor A, mouse
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