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KMID : 0361920030330030190
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Korean Journal of Orthodontics
2003 Volume.33 No. 3 p.190 ~ p.210
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A study on the regulatory effect of p-38 MAP kianse on nitric oxide and interleuken-6 in osteoblasts
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Lee, Kyung Won/이경원
Lee, Doe Hoon/Kang, Kyung Hwa/Kim, Sang Cheol/이도훈/강경화/김상철
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Abstract
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Tooth movement is the result of bone metabolism in the periodontium, where various cytokines take important roles. Interleukin-6(116) 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-l osteoblast cultures with combined interferon-y(IFN-y), lipopolysaccharide,(LPS) and tumor necrosis factor-a(TNF-a) induces expressions of inducible ´ iitric oxide synthase (iNOS) and IL-6, resulting in sustained releases of large amounts of NO and IL-6. However, IFN-y, LPS, and TNF-a individually induce a non-detectable or small amount of NO and IL-6 in AMC3T3E-1 osteoblasts. The role of MAPK activation in the early intracellular signal transduction involved in iI1OS 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-(4fuorophenyi)-2-(4-metylsulfinylphenyl)-5-(4pyridyl)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/IFNy- or TNF-a/IFN-y-treated MC3T3E-1 osteoblasts.
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