• J Formos Med Assoc · Aug 2018

    IL-1β induced IL-8 and uPA expression/production of dental pulp cells: Role of TAK1 and MEK/ERK signaling.

    • Szu-I Lin, Li-Deh Lin, Hsiao-Hua Chang, Mei-Chi Chang, Yin-Lin Wang, Yu-Hwa Pan, Guay-Feng Huang, Hseuh-Jen Lin, and Jiiang-Huei Jeng.
    • Department of Dentistry, Tao Yuan General Hospital, Ministry of Health and Welfare, Taoyuan City, Taiwan; Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University Medical College, Taipei, Taiwan.
    • J Formos Med Assoc. 2018 Aug 1; 117 (8): 697-704.

    Background/PurposeInterleukin 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.MethodsHuman 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.ResultsExposure 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.ConclusionIL-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.Copyright © 2018. Published by Elsevier B.V.

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