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• W1984371486 abstract "Inflammation promotes the progression of non-alcoholic steatohepatitis (NASH). Toll-like receptor 4 (TLR4) and TLR9 activation through myeloid differentiation primary response gene 88 (MyD88) and production of mature interleukin-1β (IL-1β) via inflammasome activation contribute to steatohepatitis. Here, we investigated the inter-relationship between TLR signalling and inflammasome activation in dietary steatohepatitis.Wild type (WT), TLR4- and MyD88-deficient (KO) mice received methionine-choline-deficient (MCD) or -supplemented (MCS) diets for 5 weeks and a subset was challenged with TLR9 ligand CpG-DNA.TLR4, TLR9, AIM2 (absent in melanoma 2) and NLRP3 (NLR family pyrin domain containing 3) inflammasome mRNA, and mature IL-1β protein levels were increased in MCD diet-induced steatohepatitis compared to MCS controls. TLR9 stimulation resulted in greater up-regulation of the DNA-sensing AIM2 expression and IL-1β production in livers of MCD compared to MCS diet-fed mice. High mobility group box 1 (HMGB1), a TLR9-activating danger molecule and phospho-HMGB1 protein levels were also increased in livers of MCD diet-fed mice. MyD88- but not TLR4-deficiency prevented up-regulation of AIM2, NLRP3 mRNA and IL-1β protein production in dietary steatohepatitis. Selective MyD88 deficiency either in bone marrow (BM)-derived or non-BM-derived cells attenuated hepatic up-regulation of inflammasome mRNA, caspase-1 activation and IL-1β protein production, but only BM-derived cell-specific MyD88-deficiency attenuated liver injury.Our data demonstrate that both bone marrow-derived and non-BM-derived cells contribute to inflammasome activation in a MyD88-dependent manner in dietary steatohepatitis. We show that AIM2 inflammasome expression and activation are further augmented by TLR9 ligands in dietary steatohepatitis." @default.
• W1984371486 created "2016-06-24" @default.
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• W1984371486 date "2014-04-17" @default.
• W1984371486 modified "2023-10-08" @default.
• W1984371486 title "Both bone marrow‐derived and non‐bone marrow‐derived cells contribute to <scp>AIM</scp>2 and <scp>NLRP</scp>3 inflammasome activation in a MyD88‐dependent manner in dietary steatohepatitis" @default.
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• W1984371486 doi "https://doi.org/10.1111/liv.12537" @default.
• W1984371486 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4169310" @default.
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