title: Effect of interleukin-1β on ICAM-1 expression of dental pulp cells: role of PI3K/Akt, MEK/ERK, and cyclooxygenase.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Biomedical Science Team, Chang Gung University of Science and Technology, Taoyuan, Taiwan.
authors.forename: Mei-Chi
authors.initials: MC
authors.lastname: Chang
authors.forename: Hsiu-Pin
authors.initials: HP
authors.lastname: Hung
authors.forename: Li-Deh
authors.initials: LD
authors.lastname: Lin
authors.forename: Yow-Chyun
authors.initials: YC
authors.lastname: Shyu
authors.forename: Tong-Mei
authors.initials: TM
authors.lastname: Wang
authors.forename: Hsueh-Jen
authors.initials: HJ
authors.lastname: Lin
authors.forename: Chiu-Po
authors.initials: CP
authors.lastname: Chan
authors.forename: Chih-Chia
authors.initials: CC
authors.lastname: Huang
authors.forename: Jiiang-Huei
authors.initials: JH
authors.lastname: Jeng
mesh_terms: D001241:Aspirin / Q000494:pharmacology; D015153:Blotting, Western; D002867:Chromones / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D003782:Dental Pulp / Q000166:cytology*; D004797:Enzyme-Linked Immunosorbent Assay; D005054:Eugenol / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D053583:Interleukin-1beta / Q000494:pharmacology*; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D002867:Chromones; D053583:Interleukin-1beta; D009025:Morpholines; D018799:Intercellular Adhesion Molecule-1; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D005054:Eugenol; D051546:Cyclooxygenase 2; D019869:Phosphatidylinositol 3-Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D001241:Aspirin