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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2006.1
- 수록면
- 417 - 427 (11page)
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To elucidate the roles of 8-hydroxydeoxyguanosine (oh8dG), the nucleoside of 8-hydroxyguanine (oh8Gua), we examined the effects of oh8dG upon LPS-induced intercellular adhesion molecule-1 (ICAM-1) ex-ng mechanisms in brain microglial cells. We found that oh8dG reduces LPS-induced reactive oxygen species (ROS) pro-duction, STAT3 activation, and ICAM-1 expresion. oh8dG also suppresses pro-inflamatory cytokines, such as TNF-α, IL-6 and IFN-γ. Overexpression of dominant negative STAT3 completely diminshed STAT3-mediated ICAM-1 transcriptional activity. Chromatin immunoprecipitation studies revealed that oh8dG inhibited recruitment of STAT3 to the ICAM-1 promoter, followed by a decrease in ICAM-1 expression. Using mice lacking a functional Toll-like TLR4+/+microglia were activated by LPS, TLR4-/- microglia exhibited inactivated STAT3 in response to LPS. Evidently, LPS modulates STAT3-dependent ICAM-1 induction through TLR4-mdiated cellular responses. Oh8dG apparently plays a role in anti- inflammatory actions via suppression of ICAM-1 gene expression by blockade of the TLR4-STAT3 signal cascade in inflammation-enhanced brain microglia. Therefore, oh8dG in the cytosol probably functions as an anti-inflammatory molecule and should be considered as a candidate for development of anti- inflammatory agents.
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참고문헌 (27)
참고문헌 신청
/ / Van der Saag P. Stimulation of the human inter-cellular adhesion molecule-1 promoter by interleukin-6 and in-terferon-gamma involves binding of distinct factors to a pali
/ / Yu BP. Protection of DNA damage by dietary restriction. Free Radic Biol Med 1992 : 523 ~ 5
/ / a novel IFN-stimulated gene factor 3 p91-related transcription factor involved in the gp130-mediated signaling pathway. Cell 1994 : 63 ~ 71
/ 1995 / Adhesion molecule expression on murine cerebral endothelium following the injection of a proin-flammagen or during acute neuronal degeneration. 24 : 695 ~ 710
/ 1996 / Increased oxidative DNA damage in Helicobacter pylori-infected human gastric mucosa. 56 : 1279 ~ 82
/ / Yu BP. Protection of DNA damage by dietary restriction. Free Radic Biol Med 1992 : 523 ~ 5
/ / a novel IFN-stimulated gene factor 3 p91-related transcription factor involved in the gp130-mediated signaling pathway. Cell 1994 : 63 ~ 71
/ 1995 / Adhesion molecule expression on murine cerebral endothelium following the injection of a proin-flammagen or during acute neuronal degeneration. 24 : 695 ~ 710
/ 1996 / Increased oxidative DNA damage in Helicobacter pylori-infected human gastric mucosa. 56 : 1279 ~ 82
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