RETRACTED: SphK1 Regulates Proinflammatory Responses Associated with Endotoxin and Polymicrobial Sepsis (Retracted Article)

被引：114

作者：

Puneet, Padmam ^{[1
]}

Yap, Celestial T. ^{[1
]}

Wong, Lingkai ^{[2
]}

Yulin, Lam ^{[2
]}

Koh, Dow Rhoon ^{[1
]}

Moochhala, Shabbir ^{[3
]}

Pfeilschifter, Josef ^{[4
]}

Huwiler, Andrea ^{[5
]}

Melendez, Alirio J. ^{[1
,6
]}

机构：

[1] Natl Univ Singapore, Dept Physiol, Singapore 117597, Singapore

[2] Natl Univ Singapore, Dept Chem, Singapore 117543, Singapore

[3] Def Med & Environm Res Inst, DSO Natl Labs, Singapore 117510, Singapore

[4] Univ Hosp, Pharmazentrum Frankfurt, D-60590 Frankfurt, Germany

[5] Univ Bern, Inst Pharmacol, CH-3010 Bern, Switzerland

[6] Univ Glasgow, Glasgow Biomed Res Ctr, Glasgow G12 8TA, Lanark, Scotland

来源：

SCIENCE | 2010年 / 328卷 / 5983期

基金：

英国医学研究理事会;

关键词：

SPHINGOSINE KINASE 1; FC-GAMMA-RI; INFLAMMATORY RESPONSES; CECAL LIGATION; CA2+ SIGNALS; MODULATION; ACTIVATION; RECEPTOR; THERAPY; EPSILON;

D O I：

10.1126/science.1188635

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

During sepsis, activation of phagocytes leads to the overproduction of proinflammatory cytokines, causing systemic inflammation. Despite substantial information regarding the underlying molecular mechanisms that lead to sepsis, several elements in the pathway remain to be elucidated. We found that the enzyme sphingosine kinase 1 (SphK1) is up-regulated in stimulated human phagocytes and in peritoneal phagocytes of patients with severe sepsis. Blockade of SphK1 inhibited phagocyte production of endotoxin-induced proinflammatory cytokines. We observed protection against sepsis in mice treated with a specific SphK1 inhibitor that was enhanced by treatment with a broad-spectrum antibiotic. These results demonstrated a critical role for SphK1 in endotoxin signaling and sepsis-induced inflammatory responses and suggest that inhibition of SphK1 is a potential therapy for septic shock.

引用

页码：1290 / 1294

页数：5

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