Roles of p38 and ERK MAP kinases in IL-8 expression in TNF-alpha- and dexamethasone-stimulated human periodontal ligament cells.
Orthodontic tooth movement is recognized as a pro-inflammatory stressor of human periodontal ligament (hPDL) cells. However, the cell-signaling pathways linking interleukin-8 (IL-8), intercellular adhesion molecule-1 (ICAM-1), pro-inflammatory cytokines, and dexamethasone in hPDL cells have not been well elucidated. In this study, we investigated the role of mitogen-activated protein (MAP) kinases in dexamethasone- and TNF-alpha-induced IL-8 and ICAM-1 expression in hPDL cells. IL-8 production was measured by enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. MAP kinase activation and IkappaB degradation were determined by Western blot analysis, and ICAM-1 expression was determined by RT-PCR and FACS analysis. TNF-alpha increased IL-8 mRNA expression and protein secretion in a dose- and time-dependent manner. Dexamethasone suppressed TNF-alpha-induced IL-8 production in a dose-dependent manner. In addition, dexamethasone inhibited TNF-alpha-induced phosphorylation of p38 MAP kinase and extracellular-regulated kinases (ERKs), IkappaB degradation, and NF-kappaB activation. Selective inhibitors for ERKs and p38 attenuated TNF-alpha-induced IL-8 and ICAM-1 expression in the presence and absence of dexamethasone, indicating that MAP kinases play a role in the response of hDPL cells to TNF-alpha. Furthermore, these results suggest that inflammatory cytokine- and dexamethasone-induced IL-8 and ICAM-1, produced via a MAP kinase pathway, may serve as an important mediator of PDL immunoregulation involved in bone remodeling during orthodontic tooth movement.
Lee
Hwa-Jeong
HJ
Department of Oral and Maxillofacial Pathology, College of Dentistry, Wonkwang University, Iksan, Republic of Korea.
Cho
Jin-Woo
JW
Kim
Sang-Cheol
SC
Kang
Kyung-Hwa
KH
Lee
Sun-Kyung
SK
Pi
Sung-Hee
SH
Lee
Suk-Keun
SK
Kim
Eun-Cheol
EC
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D016723:Bone Remodeling / Q000502:physiology; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics*; D009971:Orthodontics, Corrective; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D015398:Signal Transduction / Q000502:physiology; D014085:Tooth Migration / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology*
D000893:Anti-Inflammatory Agents; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D003907:Dexamethasone; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases