IL-1β induced IL-8 and uPA expression/production of dental pulp cells: Role of TAK1 and MEK/ERK signaling
Journal
Journal of the Formosan Medical Association
Journal Volume
117
Journal Issue
8
Pages
697-704
Date Issued
2018
Author(s)
Lin S.-I.
Chang M.-C.
Pan Y.-H.
Lin H.-J.
Abstract
Background/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
Other Subjects
1,4 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; Zearalenone
Publisher
Elsevier B.V.
Type
journal article