Document Detail


Tripartite-motif protein 30 negatively regulates NLRP3 inflammasome activation by modulating reactive oxygen species production.
MedLine Citation:
PMID:  21048113     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-11-03
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  185     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-03     Completed Date:  2011-01-04     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7699-705     Citation Subset:  AIM; IM    
Affiliation:
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Science, Shanghai, China.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / 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:
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

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