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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2018.1
- 수록면
- 45 - 53 (9page)
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A subset of anti-dsDNA autoantibodies (autoAbs), cell-penetrating Abs, may play a pathogenic role in lupus nephritis. However, the pathogenic role(s) of the Abs has not been well explored. In this study the pathological effects of a positively charged CDR3-VH-containing and cell-penetrating anti-dsDNA monoclonal mouse autoAb 2C10 immunoglobulin G (IgG) and its recombinant VH domain were investigated in a mouse mesangial cell line with respect to activation of signaling molecules and transcription of pro-inflammatory cytokines. The IgG and VH reduced cell viability in cytotoxicity assays and delayed cell cycle progress in flow cytometric analysis. Western blotting experiments showed that they activated p38, MAPKAPK-2, RSK-1, Bcl-2 and ATF-2 in the associated pathway; RSK-1 activation was regulated by p38; p38 also activated MAPKAPK-2 and ATF-2; MAPKAPK-2 regulated RSK-1 activation, and Bcl-2 was up-regulated by RSK-1. The IgG and VH remarkably stimulated the transcription of pro-inflammatory cytokines, TNF-${\alpha}$, IL-6 and IL-$1{\beta}$ And the transcription was regulated by p38 activation. These results indicate that the cell-penetrating autoAbs such as 2C10 may play a pathogenic role in mesangial cells mainly through activation of p38 signaling pathway in combination with the stimulation of pro-inflammatory cytokine production.
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참고문헌 (40)
참고문헌 신청
Alarcon-Segovia D / 1978 / Antibody to nuclear ribonucleoprotein penetrates live human mononuclear cells through Fc receptors / Nature 271:67~69
Anjum R / 2008 / The RSK family of kinases: emerging roles in cellular signalling / Nat Rev Mol Cell Biol 9:747~758
Bhatia HS / 2017 / Alleviation of microglial activation induced by p38 MAPK/MK2/PGE2 axis by capsaicin: potential involvement of other than TRPV1 mechanism/s / Sci Rep 7:116
Bonni A / 1999 / Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and -independent mechanisms / Science 286:1358~1362
Faaber P / 1986 / Cross-reactivity of human and murine anti-DNA antibodies with heparan sulfate. The major glycosaminoglycan in glomerular basement membranes / J Clin Invest 77:1824~1830
Anjum R / 2008 / The RSK family of kinases: emerging roles in cellular signalling / Nat Rev Mol Cell Biol 9:747~758
Bhatia HS / 2017 / Alleviation of microglial activation induced by p38 MAPK/MK2/PGE2 axis by capsaicin: potential involvement of other than TRPV1 mechanism/s / Sci Rep 7:116
Bonni A / 1999 / Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and -independent mechanisms / Science 286:1358~1362
Faaber P / 1986 / Cross-reactivity of human and murine anti-DNA antibodies with heparan sulfate. The major glycosaminoglycan in glomerular basement membranes / J Clin Invest 77:1824~1830
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