Effect of interleukin-1β on ICAM-1 expression of dental pulp cells: role of PI3K/Akt, MEK/ERK, and cyclooxygenase
Journal
Clinical Oral Investigations
Journal Volume
19
Journal Issue
1
Pages
117-126
Date Issued
2015
Author(s)
Chang M.-C.
Hung H.-P.
Lin H.-J.
Chan C.-P.
Huang C.-C.
Abstract
Objective: Interleukin-1β (IL-1β) is an important inflammatory mediator of the dental pulp. IL-1β stimulates cyclooxygenase-2 (COX-2) expression and prostanoid production of pulp cells and affects the inflammatory and healing processes of the dental pulp. There are two interleukin-1 (IL-1) receptors, IL-1RI and IL-1RII, with opposing effect after activation. However, the expression of IL-1Rs, the effects of IL-1β on intercellular adhesion molecule-1 (ICAM-1) of dental pulp cells, and its relation to protein kinase B (Akt) signaling and COX activation are not clear. Method: Human dental pulp cells were treated with IL-1β with/without pretreatment and co-incubation by LY294002 (a PI3K/Akt inhibitor), U0126 [a mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) inhibitor], aspirin (a COX inhibitor), or eugenol (a COX inhibitor) for different time periods. The expression of ICAM-1, IL-1RI, and IL-1RII messenger RNA (mRNA) was evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR). ICAM-1 protein expression was examined by western blotting. Soluble ICAM-1 (sICAM-1) level in the culture medium was determined by enzyme-linked immunosorbent assay (ELISA). Activation of Akt and ERK by IL-1β was measured by Pathscan p-Akt ELISA or western blot. Viable cell number was evaluated by 3-(4,5-dimethyldiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Results: Dental pulp cells expressed IL-1RI, but little IL-1RII. IL-1β stimulated COX-2 and ICAM-1 mRNA and protein expression as well as sICAM-1 production of pulp cells. Aspirin and eugenol enhanced the IL-1β-induced sICAM-1 production and ICAM-1 expression. IL-1β rapidly activated Akt and ERK. LY294002 and U0126 attenuated IL-1β-induced ICAM-1 expression and sICAM-1 production. Conclusions: These results reveal that IL-1β may be involved in the pulpal inflammatory processes by stimulating ICAM-1 expression and secretion. These events are associated with IL-1RI expression and differential activation of PI3K/Akt and MEK/ERK and COX. Clinical relevance: Pharmacological inhibition of IL-1β, IL-1RI, COX-2, ICAM-1, and related signaling pathways (MEK/ERK and PI3K/Akt) may be useful for the control of pulpal inflammation.
Publisher
Springer Verlag
Type
journal article