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SQSTM1 expression by macrophages is induced in response to environmental stresses; however, its role in macrophage\u2010mediated host responses to environmental stimuli, such as infectious pathogens, remains unclear. In this study, we investigated the role of SQSTM1 in host responses to <jats:italic>Legionella pneumophila<\/jats:italic>, an intra\u2010cellular pathogen that infects macrophages, in both an SQSTM1\u2010deficient (<jats:italic>SQSTM1<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic>) mouse model and macrophages from these mice. Compared with wild\u2010type (WT) macrophages, the production and secretion of the proinflammatory cytokine IL\u20101\u03b2 was significantly enhanced in <jats:italic>SQSTM1<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> macrophages after infection with <jats:italic>L. pneumophila<\/jats:italic>. Inflammasome activity, indicated by the level of IL\u201018 and caspase\u20101 activity, was also elevated in <jats:italic>SQSTM1<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> macrophages after infection with <jats:italic>L. pneumophila<\/jats:italic>. SQSTM1 may interact with nucleotide\u2010binding oligomerization domain\u2010like receptor family, caspase recruitment domain\u2010containing 4 and nucleotide\u2010binding oligomerization domain like receptor family, pyrin domain containing 3 proteins to inhibit their self\u2010dimerization. Acute pulmonary inflammation induced by <jats:italic>L. pneumophila<\/jats:italic> and silica was enhanced in <jats:italic>SQSTM1<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> mice with an increase in IL\u20101\u03b2 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.<\/jats:p>","DOI":"10.1002\/eji.201344091","type":"journal-article","created":{"date-parts":[[2013,12,27]],"date-time":"2013-12-27T10:16:42Z","timestamp":1388139402000},"page":"1084-1092","source":"Crossref","is-referenced-by-count":15,"title":["SQSTM1\/p62\/A170 regulates the severity of <i>Legionella pneumophila<\/i> pneumonia by modulating inflammasome activity"],"prefix":"10.1002","volume":"44","author":[{"given":"Shigeo","family":"Ohtsuka","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine Graduate School of Comprehensive Human Sciences University of Tsukuba  Tsukuba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukio","family":"Ishii","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Graduate School of Comprehensive Human Sciences University of Tsukuba  Tsukuba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Matsuyama","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Graduate School of Comprehensive Human Sciences University of Tsukuba  Tsukuba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Ano","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Graduate School of Comprehensive Human Sciences University of Tsukuba  Tsukuba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Morishima","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Graduate School of Comprehensive Human Sciences University of Tsukuba  Tsukuba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Yanagawa","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery Graduate School of Comprehensive Human Sciences University of Tsukuba  Tsukuba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiji","family":"Warabi","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Physiology Graduate School of Comprehensive Human Sciences University of Tsukuba  Tsukuba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuyuki","family":"Hizawa","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Graduate School of Comprehensive Human Sciences University of Tsukuba  Tsukuba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,1,28]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2000-9862"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2006.11.005"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-007-0078-z"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12223-010-0084-8"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.05.007"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.12.5991"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/10715769900300921"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2012.07.004"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(03)00403-9"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2006.01.011"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2008.02.001"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1348-0421.2001.tb02655.x"},{"key":"e_1_2_7_14_1","doi-asserted-by":"crossref","first-page":"712","DOI":"10.4049\/jimmunol.153.2.712","article-title":"NF\u2010kappa B regulates IL\u20101 beta transcription through a consensus NF\u2010kappa B binding site and a nonconsensus CRE\u2010like site","volume":"153","author":"Cogswell J. 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