共 24 条
Suppression of Interleukin-33 Bioactivity through Proteolysis by Apoptotic Caspases
被引:586
作者:
Luethi, Alexander U.
[1
]
Cullen, Sean P.
[1
]
McNeela, Edel A.
[2
]
Duriez, Patrick J.
[1
]
Afonina, Inna S.
[1
]
Sheridan, Clare
[1
]
Brumatti, Gabriela
[1
]
Taylor, Rebecca C.
[1
]
Kersse, Kristof
[3
,4
]
Vandenabeele, Peter
[3
,4
]
Lavelle, Ed C.
[2
]
Martin, Seamus J.
[1
]
机构:
[1] Trinity Coll Dublin, Smurfit Inst, Dept Genet, Mol Cell Biol Lab, Dublin 2, Ireland
[2] Trinity Coll Dublin, Sch Biochem & Immunol, Adjuvant Res Grp, Dublin 2, Ireland
[3] Univ Ghent VIB, Dept Mol Biomed Res, B-9052 Ghent, Belgium
[4] Univ Ghent, Dept Biomed Mol Biol, B-9052 Ghent, Belgium
来源:
基金:
爱尔兰科学基金会;
关键词:
RECEPTOR ACCESSORY PROTEIN;
INNATE IMMUNE-SYSTEM;
T-CELLS;
INFLAMMATORY CASPASES;
MAST-CELLS;
IL-33;
ST2;
ACTIVATION;
CYTOKINE;
EXPRESSION;
D O I:
10.1016/j.immuni.2009.05.007
中图分类号:
R392 [医学免疫学];
Q939.91 [免疫学];
学科分类号:
100102 ;
摘要:
Interleukin-33 (IL-33) is a member of the IL-1 family and is involved in polarization of T cells toward a T helper 2 (Th2) cell phenotype. IL-33 is thought to be activated via caspase-1-dependent proteolysis, similar to the proinflammatory cytokines IL-1 beta and IL-1 8, but this remains unproven. Here we showed that IL-33 was processed by caspases activated during apoptosis (caspase-3 and -7) but was not a physiological substrate for caspases associated with inflammation (caspase-1, -4, and -5). Furthermore, caspase-dependent processing of IL-33 was not required for ST2 receptor binding or ST2-dependent activation of the NF-kappa B transcription factor. Indeed, caspase-dependent proteolysis of IL-33 dramatically attenuated IL-33 bioactivity in vitro and in vivo. These data suggest that IL-33 does not require proteolysis for activation, but rather, that IL-33 bioactivity is diminished through caspase-dependent proteolysis within apoptotic cells. Thus, caspase-mediated proteolysis acts as a switch to dampen the proinflammatory properties of IL-33.
引用
收藏
页码:84 / 98
页数:15
相关论文