Nicotinamide adenine dinucleotide phosphate (reduced) oxidase 2 modulates inflammatory vigor during nonalcoholic fatty liver disease progression in mice

Hepatology Communications
Rajib MukherjeeSenad Divanovic

Abstract

Nonalcoholic fatty liver disease (NAFLD) represents a disease spectrum ranging from benign steatosis to life-threatening cirrhosis and hepatocellular carcinoma. Elevated levels of reactive oxygen species (ROS) and exacerbated inflammatory responses have been implicated in NAFLD progression. Nicotinamide adenine dinucleotide phosphate (reduced) oxidase 2 (NOX2; also known as gp91Phox), the main catalytic subunit of the nicotinamide adenine dinucleotide phosphate (reduced) oxidase complex, modulates ROS production, immune responsiveness, and pathogenesis of obesity-associated metabolic derangements. However, the role of NOX2 in the regulation of immune cell function and inflammatory vigor in NAFLD remains underdefined. Here, we demonstrate that obesogenic diet feeding promoted ROS production by bone marrow, white adipose tissue, and liver immune cells. Genetic ablation of NOX2 impeded immune cell ROS synthesis and was sufficient to uncouple obesity from glucose dysmetabolism and NAFLD pathogenesis. Protection from hepatocellular damage in NOX2-deficient mice correlated with reduced hepatic neutrophil, macrophage, and T-cell infiltration, diminished production of key NAFLD-driving proinflammatory cytokines, and an inherent reducti...Continue Reading

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Citations

Mar 29, 2019·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Calvin C ChanSenad Divanovic
Jan 15, 2020·Critical Reviews in Clinical Laboratory Sciences·Samir SofticC Ronald Kahn
Jan 11, 2020·Frontiers in Immunology·Jarren R OatesSenad Divanovic
May 20, 2021·Nature Communications·Calvin C ChanSenad Divanovic
Jun 9, 2021·Nutrition & Diabetes·Maria E Moreno-FernandezSenad Divanovic

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Methods Mentioned

BETA
flow cytometry
light microscopy

Software Mentioned

Gen5
SoftMax Pro
GraphPad
FlowJo
Prism

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