RESUMO
Mechanosensitive (MS) neurons in the periodontal ligament (PDL) pass information to the trigeminal ganglion when excited by mechanical stimulation of the tooth. During occlusal tooth trauma of PDL tissues, MS neurons are injured, resulting in atrophic neurites and eventual degeneration of MS neurons. Nerve growth factor (NGF), a neurotrophic factor, serves important roles in the regeneration of injured sensory neurons. In the present study, the effect of proinflammatory cytokines, including interleukin 1ß (IL1ß) and tumor necrosis factor α (TNFα), on transforming growth factor ß1 (TGFß1)induced NGF expression was evaluated in rat PDLderived SCDC2 cells. It was observed that TGFß1 promoted NGF expression via Smad2/3 and p38 mitogenactivated protein kinase (MAPK) activation. IL1ß and TNFα suppressed the TGFß1induced activation of Smad2/3 and p38 MAPK, resulting in the abrogation of NGF expression. NGF secreted by TGFß1treated SCDC2 cells promoted neurite extension and the expression of tyrosine hydroxylase, a ratelimiting enzyme in dopamine synthesis in rat pheochromocytoma PC12 cells. These results suggested that proinflammatory cytokines suppressed the TGFßmediated expression of NGF in PDLderived fibroblasts through the inactivation of TGFßinduced Smad2/3 and p38 MAPK signaling, possibly resulting in the disturbance of the regeneration of injured PDL neurons.