The Myeloid Transcription Factor KLF2 Regulates the Host Response to Polymicrobial Infection and Endotoxic Shock

被引：123

作者：

Mahabeleshwar, Ganapati H. ^{[1
]}

Kawanami, Daiji ^{[1
]}

Sharma, Nikunj ^{[1
]}

Takami, Yoichi ^{[1
]}

Zhou, Guangjin ^{[1
]}

Shi, Hong ^{[1
]}

Nayak, Lalitha ^{[1
]}

Jeyaraj, Darwin ^{[1
]}

Grealy, Robert ^{[2
]}

White, Mary ^{[2
]}

McManus, Ross ^{[2
]}

Ryan, Thomas ^{[2
]}

Leahy, Patrick ^{[3
]}

Lin, Zhiyong ^{[1
]}

Haldar, Saptarsi M. ^{[1
]}

Atkins, G. Brandon ^{[1
]}

Wong, Hector R. ^{[4
,5
]}

Lingrel, Jerry B. ^{[6
]}

Jain, Mukesh K. ^{[1
]}

机构：

[1] Case Western Reserve Univ, Sch Med, Univ Hosp Case Med Ctr,Case Cardiovasc Res Inst, Harrington McLaughlin Heart & Vasc Inst,Dept Med, Cleveland, OH 44106 USA

[2] Trinity Coll Dublin, Inst Mol Med, Dept Anesthesia, Dublin 8, Ireland

[3] Case Western Reserve Univ, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA

[4] Univ Cincinnati, Coll Med, Cincinnati Childrens Res Fdn, Div Crit Care Med, Cincinnati, OH 45267 USA

[5] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH 45267 USA

[6] Univ Cincinnati, Coll Med, Dept Mol Genet Biochem & Microbiol, Cincinnati, OH 45267 USA

来源：

IMMUNITY | 2011年 / 34卷 / 05期

基金：

美国国家卫生研究院;

关键词：

NF-KAPPA-B; INDUCIBLE FACTOR 1-ALPHA; PROINFLAMMATORY ACTIVATION; ALTERNATIVE ACTIVATION; SEVERE SEPSIS; SEPTIC SHOCK; EXPRESSION; ENDOTHELIUM; HIF-1-ALPHA; MACROPHAGES;

D O I：

10.1016/j.immuni.2011.04.014

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Precise control of myeloid cell activation is required for optimal host defense. However, this activation process must be under exquisite control to prevent uncontrolled inflammation. Herein, we identify the Kruppel-like transcription factor 2 (KLF2) as a potent regulator of myeloid cell activation in vivo. Exposure of myeloid cells to hypoxia and/or bacterial products reduced KLF2 expression while inducing hypoxia inducible factor-1 alpha (HIF-1 alpha), findings that were recapitulated in human septic patients. Myeloid KLF2 was found to be a potent inhibitor of nuclear factor-kappaB (NF-kappa B)-dependent HIF-1 alpha. transcription and, consequently, a critical determinant of outcome in models of polymicrobial infection and endotoxemia. Collectively, these observations identify KLF2 as a tonic repressor of myeloid cell activation in vivo and an essential regulator of the innate immune system.

引用

页码：715 / 728

页数：14

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