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Two of these cytokines, interleukin-1<jats:italic>\u03b2<\/jats:italic>(IL-1<jats:italic>\u03b2<\/jats:italic>) and IL-18, require activation of caspase-1 via members of the NOD-like receptor (NLR) family. These NLRs form an inflammasome that is activated by pathogens and signals released through local tissue injury or death. NLR family pyrin domain containing 3 (Nlrp3) and NLR family CARD domain containing protein 4 (Nlrc4) have been studied minimally for their role in the development of ALD. Using mice with gene targeted deletions for Nlrp3 (Nlrp3<jats:sup>\u2212\/\u2212<\/jats:sup>) and Nlrc4 (Nlrc4<jats:sup>\u2212\/\u2212<\/jats:sup>), we analyzed the response to chronic alcohol consumption. We found that Nlrp3<jats:sup>\u2212\/\u2212<\/jats:sup>mice have more severe liver injury with higher plasma alanine aminotransferase (ALT) levels, increased activation of IL-18, and reduced activation of IL-1B. In contrast, the Nlrc4<jats:sup>\u2212\/\u2212<\/jats:sup>mice had similar alcohol-induced liver injury compared to C57BL\/6J (B6) mice but had greatly reduced activation of IL-1<jats:italic>\u03b2<\/jats:italic>. This suggests that Nlrp3 and Nlrc4 inflammasomes activate IL-1<jats:italic>\u03b2<\/jats:italic>and IL-18 via caspase-1 in a differential manner. We conclude that the Nlrp3 inflammasome is protective during alcohol-induced liver injury.<\/jats:p>","DOI":"10.1155\/2013\/751374","type":"journal-article","created":{"date-parts":[[2013,12,16]],"date-time":"2013-12-16T16:03:30Z","timestamp":1387209810000},"page":"1-12","source":"Crossref","is-referenced-by-count":55,"title":["Alcohol-Induced Liver Injury Is Modulated by Nlrp3 and Nlrc4 Inflammasomes in Mice"],"prefix":"10.1155","volume":"2013","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8772-8675","authenticated-orcid":true,"given":"David A.","family":"DeSantis","sequence":"first","affiliation":[{"name":"Departments of Nutrition, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0174-1022","authenticated-orcid":true,"given":"Chih-wei","family":"Ko","sequence":"additional","affiliation":[{"name":"Departments of Nutrition, Case Western 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