RETRACTED: The cytokine interleukin-33 mediates anaphylactic shock (Retracted article. See vol. 109, pg. 15527, 2012)

被引:228
作者
Pushparaj, Peter N. [1 ]
Tay, Hwee Kee [1 ]
H'ng, Shiau Chen [2 ]
Pitman, Nick [1 ]
Xu, Damo [1 ]
McKenzie, Andrew [3 ]
Liew, Foo Y. [1 ]
Melendez, Alirio J. [1 ,2 ]
机构
[1] Univ Glasgow, Glasgow Biomed Res Ctr, Div Immunol Infect & Inflammat, Glasgow G12 8QQ, Lanark, Scotland
[2] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Physiol, Singapore 117595, Singapore
[3] MRC, Mol Biol Lab, Cambridge CB2 2QH, England
基金
英国医学研究理事会; 英国惠康基金;
关键词
anaphylaxis; cytokine biology; IL-33; FC-EPSILON-RI; NF-KAPPA-B; MAST-CELLS; GAMMA-RI; IL-13; PRODUCTION; RECEPTOR; IL-33; IGE; ST2; EXPRESSION;
D O I
10.1073/pnas.0901206106
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
Anaphylactic shock is characterized by elevated immunoglobulin-E (IgE) antibodies that signal via the high affinity Fc epsilon receptor (Fc epsilon RI) to release inflammatory mediators. Here we report that the novel cytokine interleukin-33 (IL-33) potently induces anaphylactic shock in mice and is associated with the symptom in humans. IL-33 is a new member of the IL-1 family and the ligand for the orphan receptor ST2. In humans, the levels of IL-33 are substantially elevated in the blood of atopic patients during anaphylactic shock, and in inflamed skin tissue of atopic dermatitis patients. In murine experimental atopic models, IL-33 induced antigen-independent passive cutaneous and systemic anaphylaxis, in a T cell-independent, mast cell-dependent manner. In vitro, IL-33 directly induced degranulation, strong eicosanoid and cytokine production in IgE-sensitized mast cells. The molecular mechanisms triggering these responses include the activation of phospholipase D1 and sphingosine kinase1 to mediate calcium mobilization, Nuclear factor-kappa B activation, cytokine and eicosanoid secretion, and degranulation. This report therefore reveals a hitherto unrecognized pathophysiological role of IL-33 and suggests that IL-33 may be a potential therapeutic target for anaphylaxis, a disease of considerable unmet medical need.
引用
收藏
页码:9773 / 9778
页数:6
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