Lin S.-I.LI-DEH LINChang M.-C.HSIAO-HUA CHANGYIN-LIN WANGPan Y.-H.GUAY-FEN HUANGLin H.-J.JIIANG-HUEI JENG2021-07-052021-07-0520180929-6646https://www.scopus.com/inward/record.uri?eid=2-s2.0-85046118294&doi=10.1016%2fj.jfma.2018.04.003&partnerID=40&md5=0f5bb6ceaa0805c694472d2f372acc43https://scholars.lib.ntu.edu.tw/handle/123456789/569264Background/purpose: Interleukin 1 beta (IL-1β) is a pro-inflammatory cytokine involved in the inflammatory processes of dental pulp. IL-8 and urokinase plasminogen activator (uPA) are two inflammatory mediators. However, the role of transforming growth factor beta-activated kinase-1 (TAK1) and mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathways in responsible for the effects of IL-1β on IL-8 and uPA expression/secretion of dental pulp cells are not clear. Methods: Human dental pulp cells were exposed to IL-1β with/without pretreatment with 5z-7-oxozeaneaeol (a TAK1 inhibitor) or U0126 (a MEK/ERK inhibitor). TAK1 activation was determined by immunofluorescent staining. The protein expression of IL-8 was tested by western blot. The expression of IL-8 and uPA mRNA was studied by reverse transcriptase-polymerase chain reaction (RT-PCR). The secretion of IL-8 and uPA was measured by enzyme-linked immunosorbent assay. Results: Exposure of dental pulp cells to IL-1β (0.1–10 ng/ml) stimulated IL-8 and uPA expression. IL-1β also induced IL-8 and uPA secretion of dental pulp cells. IL-1β stimulated p-TAK1 activation of pulp cells. Pretreatment and co-incubation of pulp cells by 5z-7oxozeaenol (1 and 2.5 μM) and U0126 (10 and 20 μM) prevented the IL-1β-induced IL-8 and uPA expression. 5z-7oxozeaenol and U0126 also attenuated the IL-1β-induced IL-8 and uPA secretion. Conclusion: IL-1β is important in the pathogenesis of pulpal inflammatory diseases and repair via stimulation of IL-8 and uPA expression and secretion. These events are associated with TAK1 and MEK/ERK signaling. Blocking of TAK1 and MEK/ERK signaling has potential to control inflammation of dental pulp. ? 2018[SDGs]SDG31,4 diamino 1,4 bis(2 aminophenylthio) 2,3 dicyanobutadiene; 5z 7 oxozeaneaeol; interleukin 1beta; interleukin 8; messenger RNA; mitogen activated protein kinase; mitogen activated protein kinase kinase; protein serine threonine kinase inhibitor; transforming growth factor beta activated kinase 1; unclassified drug; urokinase; 1,3 butadiene; 5-7-oxo-zeaenol; acetyl-lysyl-prolyl-seryl-seryl-prolyl-prolyl-glutamyl-glutamic acid amide; enzyme inhibitor; IL8 protein, human; interleukin 1beta; interleukin 8; MAP kinase kinase kinase 7; mitogen activated protein kinase kinase kinase; nitrile; peptide fragment; urokinase; zearalenone; Article; cellular secretion; enzyme linked immunospot assay; human; human cell; human tissue; immunofluorescence test; protein expression; protein phosphorylation; reverse transcription polymerase chain reaction; signal transduction; tooth pulp; analogs and derivatives; cell culture; cytology; drug effect; epithelium cell; MAPK signaling; metabolism; tooth pulp; Butadienes; Cells, Cultured; Dental Pulp; Enzyme Inhibitors; Epithelial Cells; Humans; Interleukin-1beta; Interleukin-8; MAP Kinase Kinase Kinases; MAP Kinase Signaling System; Nitriles; Peptide Fragments; Urokinase-Type Plasminogen Activator; Zearalenonejournal article10.1016/j.jfma.2018.04.003297093402-s2.0-85046118294