Nicotine effect on inflammatory and growth factor responses in murine cutaneous wound healing
Sofia Xanthoulea1, An Deliaert, Andrea Romano
1Department 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.
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.
Insights
Nicotine minimally impacted skin inflammation but reduced key growth factors like VEGF and TGF-β in mice. This suggests nicotine
Area of Science:
- Wound healing research
- Cutaneous injury mechanisms
- Cellular biology of inflammation
Background:
- Nicotine is a primary component of tobacco products.
- Tobacco use is linked to impaired wound healing.
- The specific molecular mechanisms of nicotine's effect on skin repair are not fully understood.
Purpose of the Study:
- To investigate nicotine's impact on the inflammatory phase of cutaneous wound healing in mice.
- To examine nicotine's effects on inflammatory mediators and growth factors in vivo and in vitro.
- To explore the role of nicotinic acetylcholine receptors (nAChRs) in nicotine's cellular actions.
Main Methods:
- Full-thickness excisional skin wounds were created in a mouse model.
- Nicotine or saline was injected into wounds.
- Expression of inflammatory mediators (TNF, IL-6, IL-12) and growth factors (VEGF, PDGF, TGF-β) was analyzed.
- In vitro studies used bone marrow-derived macrophages, resident peritoneal macrophages, and RAW 264.7 cells.
- NF-κB activity and nAChR subunit expression were assessed.
Main Results:
- Nicotine minimally affected inflammatory mediators in skin wounds.
- Nicotine significantly down-regulated growth factors (VEGF, PDGF, TGF-β) in vivo and in macrophages.
- Nicotine reduced TNF production in macrophages.
- Nicotine's effects were minimally dependent on NF-κB inhibition.
- Macrophages express the β2 nAChR subunit but not the α7 nAChR subunit.
Conclusions:
- Nicotine down-regulates crucial growth factors in skin wounds and macrophages.
- Reduced growth factor expression may contribute to the negative impact of tobacco on wound healing.
- Nicotine's effects on macrophages are partially independent of NF-κB signaling.
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