Cell Volume Regulation Modulates NLRP3 Inflammasome Activation

被引：332

作者：

Compan, Vincent ^{[1
]}

Baroja-Mazo, Alberto ^{[2
]}

Lopez-Castejon, Gloria ^{[1
]}

Gomez, Ana I. ^{[2
]}

Martinez, Carlos M. ^{[2
]}

Angosto, Diego ^{[3
]}

Montero, Maria T. ^{[4
]}

Herranz, Antonio S. ^{[4
]}

Bazan, Eulalia ^{[4
]}

Reimers, Diana ^{[4
]}

Mulero, Victoriano ^{[3
]}

Pelegrin, Pablo ^{[1
,2
]}

机构：

[1] Univ Manchester, Fac Life Sci, Manchester M13 9PT, Lancs, England

[2] Univ Hosp Virgen Arrixaca, Fdn Formac & Invest Sanitarias Reg Murcia, Ctr Invest Biomed Red Area Temat Enfermedades Hep, Inflammat & Expt Surg Unit,Murcia Biomed Res Inst, Murcia 30120, Spain

[3] Univ Murcia, Fac Biol, Dept Cell Biol & Histol, E-30100 Murcia, Spain

[4] Hosp Ramon & Cajal, Neurobiol Serv, E-28034 Madrid, Spain

来源：

IMMUNITY | 2012年 / 37卷 / 03期

基金：

英国惠康基金;

关键词：

NALP3; INFLAMMASOME; P2X(7) RECEPTOR; INTERLEUKIN-1-BETA RELEASE; CONTACT HYPERSENSITIVITY; GILTHEAD SEABREAM; KAINIC ACID; MECHANISM; CASPASE-1; CHANNEL; INJURY;

D O I：

10.1016/j.immuni.2012.06.013

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Cell volume regulation is a primitive response to alterations in environmental osmolarity. The NLRP3 inflammasome is a multiprotein complex that senses pathogen- and danger-associated signals. Here, we report that, from fish to mammals, the basic mechanisms of cell swelling and regulatory volume decrease (RVD) are sensed via the NLRP3 inflammasome. We found that a decrease in extracellular osmolarity induced a K+-dependent conformational change of the preassembled NLRP3-inactive inflammasome during cell swelling, followed by activation of the NLRP3 inflammasome and caspase-1, which was controlled by transient receptor potential channels during RVD. Both mechanisms were necessary for interleukin-1 beta processing. Increased extracellular osmolarity prevented caspase-1 activation by different known NLRP3 activators. Collectively, our data identify cell volume regulation as a basic conserved homeostatic mechanism associated with the formation of the NLRP3 inflammasome and reveal a mechanism for NLRP3 inflammasome activation.

引用

页码：487 / 500

页数：14

共 52 条

[41] Interleukin-1 and neuronal injury: mechanisms, modification, and therapeutic potential [J].