{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T17:43:09Z","timestamp":1791394989220,"version":"4.3.3"},"reference-count":45,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2014,4,17]],"date-time":"2014-04-17T00:00:00Z","timestamp":1397692800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH","award":["AA017729"],"award-info":[{"award-number":["AA017729"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2014,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background &amp; Aims<\/jats:title><jats:p>Inflammation promotes the progression of non\u2010alcoholic steatohepatitis (<jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content>). Toll\u2010like receptor 4 (<jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>4) and <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>9 activation through myeloid differentiation primary response gene 88 (MyD88) and production of mature interleukin\u20101\u03b2 (<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101\u03b2) via inflammasome activation contribute to steatohepatitis. Here, we investigated the inter\u2010relationship between <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content> signalling and inflammasome activation in dietary steatohepatitis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Wild type (<jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content>), <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>4\u2010 and MyD88\u2010deficient (<jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content>) mice received methionine\u2010choline\u2010deficient (<jats:styled-content style=\"fixed-case\">MCD<\/jats:styled-content>) or \u2010supplemented (<jats:styled-content style=\"fixed-case\">MCS<\/jats:styled-content>) diets for 5\u00a0weeks and a subset was challenged with <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>9 ligand CpG\u2010<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>TLR4, TLR9, AIM2 (absent in melanoma 2) and NLRP3 (NLR family pyrin domain containing 3) inflammasome <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>, and mature IL\u20101\u03b2 protein levels were increased in MCD diet\u2010induced steatohepatitis compared to MCS controls. TLR9 stimulation resulted in greater up\u2010regulation of the DNA\u2010sensing AIM2 expression and IL\u20101\u03b2 production in livers of MCD compared to MCS diet\u2010fed mice. High mobility group box 1 (HMGB1), a TLR9\u2010activating danger molecule and phospho\u2010HMGB1 protein levels were also increased in livers of MCD diet\u2010fed mice. MyD88\u2010 but not TLR4\u2010deficiency prevented up\u2010regulation of AIM2, NLRP3 <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> and IL\u20101\u03b2 protein production in dietary steatohepatitis. Selective MyD88 deficiency either in bone marrow (BM)\u2010derived or non\u2010BM\u2010derived cells attenuated hepatic up\u2010regulation of inflammasome <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>, caspase\u20101 activation and IL\u20101\u03b2 protein production, but only BM\u2010derived cell\u2010specific MyD88\u2010deficiency attenuated liver injury.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our data demonstrate that both bone marrow\u2010derived and non\u2010<jats:styled-content style=\"fixed-case\">BM<\/jats:styled-content>\u2010derived cells contribute to inflammasome activation in a MyD88\u2010dependent manner in dietary steatohepatitis. We show that <jats:styled-content style=\"fixed-case\">AIM<\/jats:styled-content>2 inflammasome expression and activation are further augmented by <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>9 ligands in dietary steatohepatitis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.12537","type":"journal-article","created":{"date-parts":[[2014,3,20]],"date-time":"2014-03-20T19:05:07Z","timestamp":1395342307000},"page":"1402-1413","source":"Crossref","is-referenced-by-count":87,"title":["Both bone marrow\u2010derived and non\u2010bone marrow\u2010derived cells contribute to <scp>AIM<\/scp>2 and <scp>NLRP<\/scp>3 inflammasome activation in a MyD88\u2010dependent manner in dietary steatohepatitis"],"prefix":"10.1111","volume":"34","author":[{"given":"Timea","family":"Csak","sequence":"first","affiliation":[{"name":"Department of Medicine University of Massachusetts Medical School Worcester MA 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