Substance P activates p38 mitogen-activated protein kinase to promote IL-6 induction in human dental pulp fibroblasts.
Substance P (SP) induces the expression of proinflammatory cytokines, such as interleukin (IL)-6, which are implicated in pulp inflammation. To determine the signal pathway of SP-induced IL-6, we examined the activities of the mitogen-activated protein kinases (MAPKs) in human dental pulp cell (PF-10) cultures. SP induced the phosphorylation of p38 MAPK within 5 min; this activation persisted for up to 40 min and was independent of the activation of extracellular signal-related kinases (ERK-1 and ERK-2) that were induced after SP stimulation of PF-10 cells. As shown by electrophoretic mobility shift assay p38 MAPK was not involved in SP-induced activation of nuclear factor-kappa B (NF-kappaB). However, p38 MAPK mediated SP-induced IL-6 production, as shown by the use of specific inhibitors of this kinase. Our results suggest that the activation of p38 MAPK is important for NF-kappaB-independent regulator of neurogenic inflammation in dental pulp tissues.
Tokuda
Masayuki
M
Department of Restorative Dentistry and Endodontology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan. mas-tok@dentb.hal.kagoshima-u.ac.jp
Miyamoto
Rie
R
Sakuta
Tetsuya
T
Nagaoka
Shigetaka
S
Torii
Mitsuo
M
D000328:Adult; D002478:Cells, Cultured; D003782:Dental Pulp / Q000187:drug effects* / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D005347:Fibroblasts; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D015850:Interleukin-6; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D013373:Substance P; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases