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10.1016/j.jhep.2015.11.020 http://scihub22266oqcxt.onion/10.1016/j.jhep.2015.11.020 C4761285!4761285!26632633     free     free     free Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 263.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 263.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 263.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 263.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       J+Hepatol 2016 ; 64 (3): 651-60 Nephropedia Template TP {{tp|p=26632633|t=2016. Alcohol stimulates macrophage activation through caspase dependent hepatocyte derived release of CD40L containing extracellular vesicles |pdf=|usr=}}{{26632633}} gab.com Text Alcohol stimulates macrophage activation through caspase dependent hepatocyte derived release of CD40L containing extracellular vesicles JO: J Hepatol http://www.kidney.de/pget.php?&tw=1&pmid=26632633 #FOAvip Background/Aims: The mechanisms by which hepatocyte exposure to alcohol activates inflammatory cells such as macrophages in alcoholic liver disease (ALD) are unclear. The role of released nano-sized membrane vesicles, termed extracellular vesicles (EV), in cell-to-cell communication has become increasingly recognized. We tested the hypothesis that hepatocytes exposed to alcohol may increase EV release to elicit macrophage activation. Methods: Primary hepatocytes or HepG2 hepatocyte cell lines overexpressing ethanol-metabolizing enzymes Alcohol dehydrogenase (HepG2ADH) or cytochrome P450 2E1 (HepG2Cyp2E1) were treated with ethanol and EV release was quantified with nanoparticle tracking analysis (NTA). EV mediated macrophage activation was monitored by analyzing inflammatory cytokines and macrophage associated mRNA expression, immunohistochemistry, biochemical serum ALT and triglycerides analysis in our in vitro macrophage activation and in vivo murine ethanol feeding studies. Results: Ethanol significantly increased EV release by 3.3 fold from HepG2Cyp2E1 cells and was associated with activation of caspase-3. Blockade of caspase activation with pharmacological or genetic approaches abrogated alcohol induced EV release. EV stimulated macrophage activation and inflammatory cytokine induction. An unbiased microarray-based approach and antibody neutralization experiments demonstrated a critical role of CD40 ligand (CD40L) in EV mediated macrophage activation. In vivo, wild-type (WT) mice receiving a pan-caspase, Rho kinase inhibitor or with genetic deletion of CD40 (CD40?/?) or the caspase-activating TRAIL receptor (TR?/?), were protected from alcohol-induced injury and associated macrophage infiltration. Moreover, serum from patients with alcoholic hepatitis (AH) showed increased levels of CD40L enriched EV. Conclusion: In conclusion, hepatocytes release CD40L containing EV in a caspase dependent manner in response to alcohol exposure which promotes macrophage activation, contributing to inflammation in ALD. Twit Text FOAVip Alcohol stimulates macrophage activation through caspase dependent hepatocyte derived release of CD40L containing extracellular vesicles ????J Hepatol http://www.kidney.de/pget.php?&tw=1&pmid=26632633 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=26632633 #FOAvip English Wikipedia <ref>{{Cite pmid|26632633}}</ref> Alcohol stimulates macrophage activation through caspase dependent hepatocyte derived release of CD40L containing extracellular vesicles #MMPMID26632633 Verma VK; Li H; Wang R; Hirsova P; Mushref M; Liu Y; Cao S; Contreras PC; Malhi H; Kamath PS; Gores GJ; Shah VH J Hepatol 2016[Mar]; 64 (3): 651-60 PMID26632633show ga Background/Aims: The mechanisms by which hepatocyte exposure to alcohol activates inflammatory cells such as macrophages in alcoholic liver disease (ALD) are unclear. The role of released nano-sized membrane vesicles, termed extracellular vesicles (EV), in cell-to-cell communication has become increasingly recognized. We tested the hypothesis that hepatocytes exposed to alcohol may increase EV release to elicit macrophage activation. Methods: Primary hepatocytes or HepG2 hepatocyte cell lines overexpressing ethanol-metabolizing enzymes Alcohol dehydrogenase (HepG2ADH) or cytochrome P450 2E1 (HepG2Cyp2E1) were treated with ethanol and EV release was quantified with nanoparticle tracking analysis (NTA). EV mediated macrophage activation was monitored by analyzing inflammatory cytokines and macrophage associated mRNA expression, immunohistochemistry, biochemical serum ALT and triglycerides analysis in our in vitro macrophage activation and in vivo murine ethanol feeding studies. Results: Ethanol significantly increased EV release by 3.3 fold from HepG2Cyp2E1 cells and was associated with activation of caspase-3. Blockade of caspase activation with pharmacological or genetic approaches abrogated alcohol induced EV release. EV stimulated macrophage activation and inflammatory cytokine induction. An unbiased microarray-based approach and antibody neutralization experiments demonstrated a critical role of CD40 ligand (CD40L) in EV mediated macrophage activation. In vivo, wild-type (WT) mice receiving a pan-caspase, Rho kinase inhibitor or with genetic deletion of CD40 (CD40?/?) or the caspase-activating TRAIL receptor (TR?/?), were protected from alcohol-induced injury and associated macrophage infiltration. Moreover, serum from patients with alcoholic hepatitis (AH) showed increased levels of CD40L enriched EV. Conclusion: In conclusion, hepatocytes release CD40L containing EV in a caspase dependent manner in response to alcohol exposure which promotes macrophage activation, contributing to inflammation in ALD. äAlcohol stimulates macrophage activation through caspase dependent hep(epmc).pdf DeepDyve Pubget Overpricing