IL-1β-induced MCP-1 expression and secretion of human dental pulp cells is related to TAK1, MEK/ERK, and PI3K/Akt signaling pathways.
OBJECTIVE
Interleukin-1β (IL-1β) is an inflammatory molecule of the dental pulp. IL-1β stimulates cyclooxygenase-2 (COX-2) and prostaglandins production of pulp cells and affects the pulpal inflammation and repair. However, the effects of IL-1β on Monocyte Chemotactic Factor-1 (MCP-1) of dental pulp cells and its relation to transforming growth factor β-activated kinase-1 (TAK1), PI3K/Akt, and MEK/ERK signaling and COX activation are not fully clear.


METHODS
Human dental pulp cells were exposed to IL-1β with/without pretreatment and co-incubation by aspirin (a COX inhibitor), 5z-7-oxozeaenol (a TAK1 inhibitor), LY294002 (a PI3K/Akt inhibitor) or U0126 (a MEK/ERK inhibitor). Viable cell number was evaluated by MTT assay. MCP-1 mRNA expression was tested by reverse transcriptase-polymerase chain reaction (RT-PCR). MCP-1 and COX-2 protein expression was studied by western blot. MCP-1 in the culture medium was measure by ELISA.


RESULTS
IL-1β showed little cytotoxicity to pulp cells. It stimulated MCP-1 mRNA and protein expression and MCP-1 secretion. Aspirin, U0126, LY294002 and 5z-7-oxozeaenol attenuated the IL-1β-induced MCP-1 expression. In addition, 5z-7-oxozeaenol, LY294002, U0126 and aspirin prevented the IL-1β-induced MCP-1 secretion of pulp cells.


CONCLUSIONS
These results indicate that IL-1β may be involved in the pulpal inflammatory and healing processes by inducing MCP-1 expression and secretion. These events are related to differential activation of TAK1, PI3K/Akt and MEK/ERK 1/2 signaling and COX activation. These results are important for future pharmacologic intervention of pulpal inflammatory diseases.
Chang Gung University of Science and Technology, Kwei-Shan, Taoyuan City, Taiwan.
Mei-Chi
MC
Chang
Graduate Institute of Clinical Dentistry & Department of Dentistry, National Taiwan University Hospital and National Taiwan University Medical College, Taiwan.
Yi-Ling
YL
Tsai
Graduate Institute of Clinical Dentistry & Department of Dentistry, National Taiwan University Hospital and National Taiwan University Medical College, Taiwan. Electronic address: hhchang.pedo@gmail.com.
Hsiao-Hua
HH
Chang
School of Dentistry, Taipei Medical University, Taiwan.
Sheng-Yang
SY
Lee
Graduate Institute of Clinical Dentistry & Department of Dentistry, National Taiwan University Hospital and National Taiwan University Medical College, Taiwan.
Ming-Shu
MS
Lee
School of Dentistry, Taipei Medical University, Taiwan.
Chun-Wei
CW
Chang
Department of Dentistry, Chang Gun Memorial Hospital, Taipei, Taiwan.
Chiu-Po
CP
Chan
Graduate Institute of Clinical Dentistry & Department of Dentistry, National Taiwan University Hospital and National Taiwan University Medical College, Taiwan.
Chien-Yang
CY
Yeh
School of Dentistry, Taipei Medical University, Taiwan.
Ru-Hsiu
RH
Cheng
Graduate Institute of Clinical Dentistry & Department of Dentistry, National Taiwan University Hospital and National Taiwan University Medical College, Taiwan. Electronic address: jhjeng@ntu.edu.tw.
Jiiang-Huei
JH
Jeng
D001241:Aspirin / Q000494:pharmacology; D015153:Blotting, Western; D002070:Butadienes / Q000494:pharmacology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism*; D002867:Chromones / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D003782:Dental Pulp / Q000166:cytology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D066298:In Vitro Techniques; D053583:Interleukin-1beta / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D009025:Morpholines / Q000494:pharmacology; D009570:Nitriles / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D015025:Zearalenone / Q000031:analogs & derivatives / Q000494:pharmacology / Q000008:administration & dosage; D007783:Lactones; D012118:Resorcinols
D001241:Aspirin; D002070:Butadienes; D018932:Chemokine CCL2; D002867:Chromones; D051546:Cyclooxygenase 2; D053583:Interleukin-1beta; D009025:Morpholines; D009570:Nitriles; D015025:Zearalenone; C505734:7-oxozeanol; D007783:Lactones; D012118:Resorcinols; C113580:U 0126; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Cyclooxygenase; Inflammation; Interleukin-1β; MCP-1; MEK/ERK; PI3K/Akt; Pulp; Signal transduction; TAK1