Critical role of transmethylation in TLR signaling and systemic lupus erythematosus

doi:10.1016/j.clim.2013.02.018

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	Critical role of transmethylation in TLR signaling and systemic lupus erythematosus
	Tardif, Virginie 2; Manenkova, Yulia 4; Berger, Michael 3; Hoebe, Kasper 2; Zuo, Jian-Ping1 ; Yuan, Chong 4; Kono, Dwight H.2; Theofilopoulos, Argyrios N.2; Lawson, Brian R.2
刊名	CLINICAL IMMUNOLOGY
	2013-05
卷号	147 期号:2 页码:133-143
关键词	Systemic lupus erythematosus Transmethylation S-adenosyl-L-homocysteine hydrolase Toll-like receptors Lymphocytes
ISSN号	1521-6616
DOI	10.1016/j.clim.2013.02.018
文献子类	Article
英文摘要	Post-translational protein modifications can play a significant role in immune cell signaling. Recently, we showed that inhibition of transmethylation curtails experimental autoimmune encephalomyelitis, notably by reducing T cell receptor (TCR)-induced activation of CD4(+) T cells. Here, we demonstrate that transmethylation inhibition by a reversible S-adenosyl-L-homocysteine hydrolase inhibitor (DZ2002) led to immunosuppression by reducing TLR-, B cell receptor (BCR)- and TCR-induced activation of immune cells, most likely by blocking NF-kappa B activity. Moreover, prophylactic treatment with DZ2002 prevented lupus-like disease from developing in both BXSB and MRL-Fas(lpr) mouse models. DZ2002 treatment initiated during active disease significantly improved outcomes in both in vivo models, suggesting methylation inhibition as a novel approach for the treatment of autoimmune/inflammatory diseases. (C) 2013 Elsevier Inc. All rights reserved.
资助项目	NIH[00000000]
WOS关键词	L-HOMOCYSTEINE HYDROLASE ; T-CELL-ACTIVATION ; PROTEIN ARGININE METHYLATION ; KAPPA-B ACTIVATION ; MURINE LUPUS ; S-ADENOSYLMETHIONINE ; MACROPHAGE ACTIVATION ; GENE-EXPRESSION ; NUCLEIC-ACID ; IFN-GAMMA
WOS研究方向	Immunology
语种	英语
出版者	ACADEMIC PRESS INC ELSEVIER SCIENCE
WOS记录号	WOS:000318328900009
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277640]
专题	药理学第一研究室
通讯作者	Lawson, Brian R.
作者单位	1.Shanghai Inst Mat Med, Shanghai, Peoples R China; 2.Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA; 3.Scripps Res Inst, Dept Genet, La Jolla, CA 92037 USA; 4.Gen Atom, Diazyme Div, San Diego, CA USA
推荐引用方式 GB/T 7714	Tardif, Virginie,Manenkova, Yulia,Berger, Michael,et al. Critical role of transmethylation in TLR signaling and systemic lupus erythematosus[J]. CLINICAL IMMUNOLOGY,2013,147(2):133-143.
APA	Tardif, Virginie.,Manenkova, Yulia.,Berger, Michael.,Hoebe, Kasper.,Zuo, Jian-Ping.,...&Lawson, Brian R..(2013).Critical role of transmethylation in TLR signaling and systemic lupus erythematosus.CLINICAL IMMUNOLOGY,147(2),133-143.
MLA	Tardif, Virginie,et al."Critical role of transmethylation in TLR signaling and systemic lupus erythematosus".CLINICAL IMMUNOLOGY 147.2(2013):133-143.