BackgroundThere is increasing popularity of high-power lasers for surgical debridement and antimicrobial therapy in the management of peri-implantitis and periodontal therapy. Removal of the noxious foci would naturally promote tissue healing directly. However, there are also anecdotal reports of better healing around routine high-power laser procedures. The precise mechanisms mediating these effects remain to be fully elucidated. This work examines these low-dose laser bystander effects on oral human epithelial and fibroblasts, particularly focusing on the role of human -defensin 2 (HBD-2 or DEFB4A), a potent factor capable of antimicrobial effects and promoting wound healing. Material and MethodsLaser treatments were performed using a near-infrared laser (810 nm diode) at low doses. Normal human oral keratinocytes and fibroblast cells were used and HBD-2 mRNA and protein expression was assessed with real time polymerase chain reaction, western blotting and immunostaining. Role of transforming growth factor (TGF)-1 signaling in this process was dissected using pathway-specific small molecule inhibitors. ResultsWe observed laser treatments robustly induced HBD-2 expression in an oral fibroblast cell line compared to a keratinocyte cell line. Low-dose laser treatments results in activation of the TGF-1 pathway that mediated HBD-2 expression. The two arms of TGF-1 signaling, Smad and non-Smad are involved in laser-mediated HBD-2 expression. ConclusionsLaser-activated TGF-1 signaling and induced expression of HBD-2, both of which are individually capable of promoting healing in tissues adjacent to high-power surgical laser applications. Moreover, the use of low-dose laser therapy itself can provide additional therapeutic benefits for effective clinical management of periodontal or peri-implant disease.