Nicotine inhibits human gingival fibroblast migration via modulation of Rac signalling pathways

Cigarette smoking is a risk factor in the development of periodontal diseases. In addition, a delayed healing process has been shown in smokers compared with non-smokers after periodontal treatment. Cell migration is a key process of wound healing and it is highly regulated by a variety of signalling pathways. The small G protein, Rac, is necessary for cell migration. Our aim was to determine if nicotine disrupted Rac and its downstream signalling proteins, p21-activated kinase 1/2 (PAK1/2), and p44/42 mitogen-activated protein kinase (MAPK) (extracellular regulated kinase 1/2). Primary human fibroblasts from healthy gingival tissues were cultured and grown to confluence. Cells were serum starved for 24 h, and then treated with nicotine (0 or 0.5 mu M) prior to in vitro wounding. Cell migration was analysed in live cell assays following in vitro wounds. Rac activity, phosphorylation levels of PAK1/2, and p44/42 MAPK were assessed in cultures treated with or without nicotine after multiple wounds. Nicotine decreased cell migration rates by 50% compared with controls. In addition, nicotine altered the activation patterns of Rac and PAK 1/2 and up-regulated p44/42 MAPK. Decreased cell migration in periodontal wounds exposed to nicotine may be mediated through the Rac and PAK1/2 signalling pathways.