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• W1566773742 abstract "Sequestosome1/A170/p62 (SQSTM1) is a scaffold multifunctional protein involved in several cellular events, such as signal transduction, cell survival, cell death, and inflammation. SQSTM1 expression by macrophages is induced in response to environmental stresses; however, its role in macrophage‐mediated host responses to environmental stimuli, such as infectious pathogens, remains unclear. In this study, we investigated the role of SQSTM1 in host responses to Legionella pneumophila , an intra‐cellular pathogen that infects macrophages, in both an SQSTM1‐deficient ( SQSTM1 −/− ) mouse model and macrophages from these mice. Compared with wild‐type (WT) macrophages, the production and secretion of the proinflammatory cytokine IL‐1β was significantly enhanced in SQSTM1 −/− macrophages after infection with L. pneumophila . Inflammasome activity, indicated by the level of IL‐18 and caspase‐1 activity, was also elevated in SQSTM1 −/− macrophages after infection with L. pneumophila . SQSTM1 may interact with nucleotide‐binding oligomerization domain‐like receptor family, caspase recruitment domain‐containing 4 and nucleotide‐binding oligomerization domain like receptor family, pyrin domain containing 3 proteins to inhibit their self‐dimerization. Acute pulmonary inflammation induced by L. pneumophila and silica was enhanced in SQSTM1 −/− mice with an increase in IL‐1β levels in the bronchoalveolar lavage fluids. These findings suggest that SQSTM1 is a negative regulator of acute pulmonary inflammation, possibly by regulating inflammasome activity and subsequent proinflammatory cytokine production." @default.
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• W1566773742 date "2014-01-28" @default.
• W1566773742 modified "2023-10-16" @default.
• W1566773742 title "SQSTM1/p62/A170 regulates the severity of<i>Legionella pneumophila</i>pneumonia by modulating inflammasome activity" @default.
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• W1566773742 doi "https://doi.org/10.1002/eji.201344091" @default.
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