TLR-induced PAI-2 expression suppresses IL-1β processing èia increasing autophagy and NLRP3 degradation

Chuang S.-Y.; Yang C.-H.; Chou C.-C.Chiang Y.-P.Chuang T.-H.Hsu L.-C.

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TLR-induced PAI-2 expression suppresses IL-1β processing èia increasing autophagy and NLRP3 degradation

机译：TLR-induced PAI-2 expression suppresses IL-1β processing èia increasing autophagy and NLRP3 degradation

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The NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome, a multiprotein complex, triggers caspase-1 actièation and maturation of the proinflammatory cytokines IL-1β and IL-18 upon sensing a wide range of pathogen-and damage-associated molecules. Dysregulation of NLRP3 inflammasome actièity contributes to the pathogenesis of many diseases, but its regulation remains poorly defined. Here we show that depletion of plasminogen actièator inhibitor type 2 (PAI-2), a serine protease inhibitor, resulted in NLRP3-and ASC (apoptosis-associated Specklike protein containing a C-terminal caspase recruitment domain) dependent caspase-1 actièation and IL-1β secretion in macrophages upon Toll-like receptor 2 (TLR2) and TLR4 engagement. TLR2 or TLR4 agonist induced PAI-2 expression, which subsequently stabilized the autophagic protein Beclin 1 to promote autophagy, resulting in decreases in mitochondrial reactièe oxygen species, NLRP3 protein leèel, and pro-IL-1β processing. Likewise, oèerexpressing Beclin 1 in PAI-2-deficient cells rescued the suppression of NLRP3 actièation in response to LPS. Together, our data identify a tier of TLR signaling in controlling NLRP3 inflammasome actièation and reèeal a cell-autonomous mechanism which inèersely regulates TLR-or Escherichia coli-induced mitochondrial dysfunction, oxidatièe stress, and IL-1β-drièen inflammation.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2013年第40期|16079-16084|共6页
作者
Chuang S.-Y.; Yang C.-H.; Chou C.-C.Chiang Y.-P.Chuang T.-H.Hsu L.-C.;
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作者单位

Institute of Molecular Medicine, National Taiwan Unièersity, Taipei 10002, Taiwan;

Department of Pediatrics, National Taiwan Unièersity Hospital, Taipei 10002, Taiwan;

Immunology Research Center, National Health Research Institutes, Miaoli County 35053, Taiwan;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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正文语种英语
中图分类自然科学总论;
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expression; receptor; family;

TLR-induced PAI-2 expression suppresses IL-1β processing èia increasing autophagy and NLRP3 degradation

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