| Tripartite-motif protein 30 negatively regulates NLRP3 inflammasome activation by modulating reactive oxygen species production. | |
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MedLine Citation:
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PMID: 21048113 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The NLR family, pyrin domain-containing 3 (NLRP3) inflammasome is critical for caspase-1 activation and the proteolytic processing of pro-IL-1β. However, the mechanism that regulates NLRP3 inflammasome activation remains unclear. In this paper, we demonstrate that tripartite-motif protein 30 (TRIM30) negatively regulates NLRP3 inflammasome activation. After stimulation with ATP, an agonist of the NLRP3 inflammasome, knockdown of TRIM30 enhanced caspase-1 activation and increased production of IL-1β in both J774 cells and bone marrow-derived macrophages. Similarly with ATP, knockdown of TRIM30 increased caspase-1 activation and IL-1β production triggered by other NLRP3 inflammasome agonists, including nigericin, monosodium urate, and silica. Production of reactive oxygen species was increased in TRIM30 knockdown cells, and its increase was required for enhanced NLRP3 inflammasome activation, because antioxidant treatment blocked excess IL-1β production. Conversely, overexpression of TRIM30 attenuated reactive oxygen species production and NLRP3 inflammasome activation. Finally, in a crystal-induced NLRP3 inflammasome-dependent peritonitis model, monosodium urate-induced neutrophil flux and IL-1β production was reduced significantly in TRIM30 transgenic mice as compared with that in their nontransgenic littermates. Taken together, our results indicate that TRIM30 is a negative regulator of NLRP3 inflammasome activation and provide insights into the role of TRIM30 in maintaining inflammatory responses. |
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Authors:
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Yu Hu; Kairui Mao; Yan Zeng; Shuzhen Chen; Zhiyun Tao; Chen Yang; Shuhui Sun; Xiaodong Wu; Guangxun Meng; Bing Sun |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-11-03 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 185 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-12-03 Completed Date: 2011-01-04 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 7699-705 Citation Subset: AIM; IM |
Affiliation:
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Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Science, Shanghai, China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine Triphosphate
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immunology,
metabolism,
pharmacology Animals Anti-Bacterial Agents / pharmacology Antioxidants / pharmacology Carrier Proteins / genetics, immunology*, metabolism Caspase 1 / genetics, immunology, metabolism HEK293 Cells Humans Inflammasomes / genetics, immunology*, metabolism Inflammation / genetics, immunology, metabolism Interleukin-1beta / genetics, immunology, metabolism Intracellular Signaling Peptides and Proteins / genetics, immunology, metabolism Mice Mice, Knockout Neutrophil Infiltration / drug effects, genetics, immunology Neutrophils / immunology, metabolism Nigericin / pharmacology Peritonitis / genetics, immunology, metabolism Reactive Oxygen Species / immunology*, metabolism Silicon Dioxide / pharmacology Uric Acid / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Anti-Bacterial Agents; 0/Antioxidants; 0/CIAS1 protein, mouse; 0/Carrier Proteins; 0/Inflammasomes; 0/Interleukin-1beta; 0/Intracellular Signaling Peptides and Proteins; 0/NLRP3 protein, human; 0/Reactive Oxygen Species; 0/TRIM30 alpha protein, mouse; 28380-24-7/Nigericin; 56-65-5/Adenosine Triphosphate; 69-93-2/Uric Acid; 7631-86-9/Silicon Dioxide; EC 3.4.22.36/Caspase 1 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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