Journal
CLINICS AND RESEARCH IN HEPATOLOGY AND GASTROENTEROLOGY
Volume 39, Issue -, Pages S24-S28Publisher
ELSEVIER MASSON, CORP OFF
DOI: 10.1016/j.clinre.2015.05.016
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Funding
- NIH [P50AA011999, R24AA12885, K01AA020524, DK048522-19]
- Medical Research Service of Department of Veterans Affairs [5IO BX001991-02F]
- ABMRF/The Foundation for Alcohol Research
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Macrophages are a key cell type in the innate immune system, and its proinflammatory (M1) activation in the liver plays a critical role in pathogenesis of alcoholic steatohepatitis. Emerging evidence indicates the involvement of Notch signaling in regulation of innate immune response and cellular metabolism. Metabolic switch to glycolysis characterizes macrophages undergoing M1 activation. It has been proposed that metabolic reprograming in response to extrinsic stimulation, such as bacterial endotoxin, triggers intrinsic signal to dictate cell differentiation. Using an obesity-alcohol synergistic ASH mouse model, we have recently shown that Notch1 pathway promotes M1 activation of hepatic macrophages, through direct upregulation of M1 gene transcription and through reprograming of mitochondrial metabolism to glucose oxidation and subsequent mtROS generation to augment M1 gene expression. Our studies demonstrate a novel mechanism of Notch1 signaling in metabolic reprograming of macrophage for M1 activation in ASH. (C) 2015 Elsevier Masson SAS. All rights reserved.
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