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Granulysin production and anticryptococcal activity is dependent upon a far upstream enhancer that binds stat5 in human peripheral blood cd4(+) t cells
Xing, Junji1; Wu, Fuqing1; Wang, Shuai1; Krensky, Alan M.2; Mody, Christopher H.3,4; Zheng, Chunfu1
刊名Journal of immunology
2010-11-01
卷号185期号:9页码:5074-5081
ISSN号0022-1767
DOI10.4049/jimmunol.1001725
通讯作者Zheng, chunfu(zheng.alan@hotmail.com)
英文摘要Previous studies have demonstrated that stat5 is critical for expression of granulysin and antimicrobial activity. because the signaling pathway and the resultant microbicidal activity are defective in hiv-infected patients, the mechanism by which stat5 leads to granulysin expression is of great interest. in the current study, il-2-stimulated crl-2105 cd4(+) t cells expressed granulysin and killed cryptococcus neoformans similar to primary cd4(+) t cells. the enhancer activity of the upstream element of the granulysin promoter was analyzed in primary cd4(+) t cells and crl-2105 t cells with a luciferase reporter assay, and a stat5 binding site, 18,302 to 18,177 bp upstream of the transcription start site, was identified as an enhancer. additionally, the enhancer functioned in the context of heterologous sv40 promoter irrespective of its transcriptional orientation. chromatin immunoprecipitation and emsas demonstrated that the enhancer element bound stat5 both in vivo and in vitro, and mutation of the stat5 binding site abrogated its enhancer activity. furthermore, overexpression of a dominant negative stat5a abolished the enhancer activity of the stat5 binding site and abrogated the anticryptococcal activity of il-2-stimulated primary cd4(+) t cells. taken together, these data provide details about the complex regulation leading to granulysin expression and anticryptococcal activity in primary cd4(+) t cells. the journal of immunology, 2010, 185: 5074-5081.
WOS关键词CRYPTOCOCCUS-NEOFORMANS ; MYCOBACTERIUM-TUBERCULOSIS ; REQUIRES GRANULYSIN ; SIGNALING PATHWAYS ; GENE-EXPRESSION ; NATURAL-KILLER ; DNA-BINDING ; IFN-ALPHA ; NK CELLS ; ACTIVATION
WOS研究方向Immunology
WOS类目Immunology
语种英语
出版者AMER ASSOC IMMUNOLOGISTS
WOS记录号WOS:000283248700020
内容类型期刊论文
URI标识http://www.corc.org.cn/handle/1471x/2375832
专题武汉病毒研究所
通讯作者Zheng, Chunfu
作者单位1.Chinese Acad Sci, Wuhan Inst Virol, State Key Lab Virol, Wuhan 430071, Peoples R China
2.NCI, Lab Cellular & Mol Biol, NIH, Bethesda, MD 20892 USA
3.Univ Calgary, Dept Internal Med, Calgary, AB T2N 4N1, Canada
4.Univ Calgary, Dept Microbiol & Infect Dis, Calgary, AB T2N 4N1, Canada
推荐引用方式
GB/T 7714
Xing, Junji,Wu, Fuqing,Wang, Shuai,et al. Granulysin production and anticryptococcal activity is dependent upon a far upstream enhancer that binds stat5 in human peripheral blood cd4(+) t cells[J]. Journal of immunology,2010,185(9):5074-5081.
APA Xing, Junji,Wu, Fuqing,Wang, Shuai,Krensky, Alan M.,Mody, Christopher H.,&Zheng, Chunfu.(2010).Granulysin production and anticryptococcal activity is dependent upon a far upstream enhancer that binds stat5 in human peripheral blood cd4(+) t cells.Journal of immunology,185(9),5074-5081.
MLA Xing, Junji,et al."Granulysin production and anticryptococcal activity is dependent upon a far upstream enhancer that binds stat5 in human peripheral blood cd4(+) t cells".Journal of immunology 185.9(2010):5074-5081.
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