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, Jiiang Huei Jeng*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

15 Scopus citations


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.

Original languageEnglish
Pages (from-to)697-704
Number of pages8
JournalJournal of the Formosan Medical Association
Issue number8
StatePublished - 08 2018
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2018


  • Dental pulp
  • Healing
  • Inflammation
  • Interleukin-1β
  • Signal transduction
  • TAK1
  • Urokinase plasminogen activator


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