Korean J Orthod.  2003 Jun;33(3):199-210.

A study on the regulatory effect of p-38 MAP kinase on nitric oxide and interleukin-6 in osteoblasts

• Lee KW
• Lee DH
• Kang KH
• Kim SC

Abstract

Tooth movement is the result of bone metabolism in the periodontium, where various cytokines take important roles. Interleukin-6(Il-6) and nitrous oxide (NO) were reported to be secreted from osteoblasts in the process of bone resorption. The mechanism of the process has not been clearly understood, but the activation of mitogen-activated protein kinase (MAPK) was known to be an important process in the release of the inflammatory cytokines in macrophages. In this regard, to prove the role of MAPK in the release of IL-6 and NO in MC3T3E-1 osteoblasts, Northern blot analysis, Western blot analysis and immune complex kinase assay were used. As a result, the treatment of MC3T3E-1 osteoblast cultures with combined interferon-gamma (IFN-gamma), lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-alpha) induces expressions of inducible nitric oxide synthase (iNOS) and IL-6, resulting in sustained releases of large amounts of NO and IL-6. However, IFN-gamma, LPS, and TNF-alpha individually induce a non-detectable or small amount of NO and IL-6 in MC3T3E-1 osteoblasts. The role of MAPK activation in the early intracellular signal transduction involved in iNOS and IL-6 transcription in the combined agents-stimulated osteoblasts has been investigated. The p38 MAPK pathway is specifically involved in the combined agents-induced NO and IL-6 release, since NO and IL-6 release in the presence of a specific inhibitor of p38 MAPK, 4-(4-fluorophenyl)-2-(4-metylsulfinylphenyl)-5-(4-pyridyl)imidazole) (SB203580), were significantly diminished. In contrast, PD98059, a specific inhibitor of MEK1, had no effect on NO and IL-6 release. Northern blot analysis showed that the p38 MAPK pathway controlled the iNOS and IL-6 transcription level. These data suggest that p38 MAPK play an important role in the secretion of NO and IL-6 in LPS/IFNgamma- or TNF-alpha/IFN-gamma-treated MC3T3E-1 osteotion of

Keyword

Osteoblast; P-38 MAP kinase; Nitric oxide; Interleukin-6

MeSH Terms

Antigen-Antibody Complex
Blotting, Northern
Blotting, Western
Bone Resorption
Cytokines
Interferon-gamma
Interleukin-6*
Macrophages
Metabolism
Nitric Oxide Synthase Type II
Nitric Oxide*
Nitrous Oxide
Osteoblasts*
p38 Mitogen-Activated Protein Kinases
Periodontium
Phosphotransferases*
Protein Kinases
Signal Transduction
Tooth Movement
Tumor Necrosis Factor-alpha
Antigen-Antibody Complex
Cytokines
Interferon-gamma
Interleukin-6
Nitric Oxide
Nitric Oxide Synthase Type II
Nitrous Oxide
Phosphotransferases
Protein Kinases
Tumor Necrosis Factor-alpha
p38 Mitogen-Activated Protein Kinases