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Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Exp+Mol+Pathol 2014 ; 97 (2): 305-13 Nephropedia Template TP
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The inflammasome in alcoholic hepatitis: its relationship with Mallory-Denk body formation #MMPMID25149528
Peng Y; French BA; Tillman B; Morgan T; French SW
Exp Mol Pathol 2014[Oct]; 97 (2): 305-13 PMID25149528show ga
Recent studies indicate that the inflammasome activation plays important roles in pathogenesis of alcoholic hepatitis (AH). Nod-like receptor protein 3 (NLRP3) is a key component of the macromolecular complex so called the inflammasome that trigger caspase 1-dependent maturation of the precursors of IL-1? and IL-18 cytokines. It is also known that the adaptor proteins including apoptosis-associated speck-like protein containing CARD (ASC) and the mitochondrial antiviral signaling protein (MAVS) are necessary for NLRP3-dependent inflammasome function. Steatohepatitis frequently includes Mallory-Denk body (MDB) formation. In the case of alcoholic steatohepatitis, MDB formation occurs in 80% of biopsies (French 1981; French 1981). While previous studies have focused on in vitro cell lines and mouse models, we are the first group to investigate inflammasome activation in AH liver biopsy specimen and correlate it with MDB formation. Expression of NOD1, NLRP3, ASC, NAIP, MAVS, Caspase 1, IL-1?, IL-18, and other inflammatory components including IL-6, IL-10, TNF-?, IFN-?, STAT3, p65 was measured in three to eight formalin-fixed paraffin-embedded AH specimens and control normal liver specimens by immunofluorescence staining and quantified by immunofluorescence intensity. The specimens were double stained with ubiquitin to demonstrate the relationship between inflammasome activation and MDB formation. MAVS, caspase1, IL-18, TNF-? showed increases in expression in AH compared to the controls (p<0.05), and NAIP expression markedly increased in AH compared to the controls (p<0.01). There was a trend that levels of NLRP3, ASC, caspase1, IL-18, IL-10, and p65 expression correlated with the number of MDBs found in the same field of measurement (correlation coefficients were between 0.62 to 0.93, p<0.05). Our results demonstrate the activation of the inflammasome in AH and suggest that MDB could be an indicator of the extent of inflammasome activation.