The role of NADPH oxidases in infectious and inflammatory diseases

Abstract

Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOX) are enzymes that generate superoxide or hydrogen peroxide from molecular oxygen utilizing NADPH as an electron donor. There are seven enzymes in the NOX family: NOX1-5 and dual oxidase (DUOX) 1–2. NOX enzymes in humans play important roles in diverse biological functions and vary in expression from tissue to tissue. Importantly, NOX2 is involved in regulating many aspects of innate and adaptive immunity, including regulation of type I interferons, the inflammasome, phagocytosis, antigen processing and presentation, and cell signaling. DUOX1 and DUOX2 play important roles in innate immune defenses at epithelial barriers. This review discusses the role of NOX enzymes in normal physiological processes as well as in disease. NOX enzymes are important in autoimmune diseases like type 1 diabetes and have also been implicated in acute lung injury caused by infection with SARS-CoV-2. Targeting NOX enzymes directly or through scavenging free radicals may be useful therapies for autoimmunity and acute lung injury where oxidative stress contributes to pathology.

Transcriptomics of single dose and repeated carbon black and ozone inhalation co-exposure highlight progressive pulmonary mitochondrial dysfunction

“…In order to clarify a potential link between the inflammatory response and mitochondrial function, we studied NADPH oxidase system alterations. NADPH oxidase system is among the best described pathways connecting inflammatory response and mitochondrial dysfunction through reactive oxygen species (ROS) production [ 81 – 85 ]. Real time PCR has recently been recommended as the method of choice for initial screening of NADPH pathway [ 86 ].…”

“…Our results clearly indicated increased mRNA expression of Nox2 as well as Duox2 subunits as well as adaptor proteins P40 phox , and P47 phox . While Nox2 is a well-known for its expression in function in phagocytes, Duox2 is highly expressed by the epithelial cell in the lungs [ 81 , 87 , 88 ]. This increase further confirm exposure induced ROS production pathway activation goes beyond the infiltrating leukocytes and point towards a tissue level biochemical/pathologic alteration.…”

“…These findings of increased ROS production are in line with our recently published immuno spin-trapping data which also confirmed presence of oxidants in macrophages as well as epithelial cells in the lungs after similar exposure ([ 90 ]. NOX derived ROS play an important role in regulating NLRP3 inflammasome (reviewed in [ 81 ]). We demonstrate an increase in IL-1β levels (Fig.…”

Inhibition of endothelial Nox2 activation by LMH001 protects mice from angiotensin II-induced vascular oxidative stress, hypertension and aortic aneurysm

“…Endothelial oxidative stress and inflammation attributable to the excess production of reactive oxygen species (ROS) by a Nox2-containing nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase, or Nox) is involved in many cardiovascular diseases such as hypertension, atherosclerosis, aortic aneurysms and heart failure [ [1] , [2] , [3] ]. The NADPH oxidase is a complex enzyme of several regulatory subunits, e.g., p40 phox , p47 phox , p67 phox and rac1 and a cytochrome b 558 (containing a catalytic Nox subunit and a p22 phox subunit) [ 1 , 4 ]. So far, seven isoforms of Nox (Nox1-5 and Duox 1–2) have been reported.…”

Antioxidant Roles of SGLT2 Inhibitors in the Kidney

“…There are seven members of the NOX family, NOX1–5 and DUOX1 and 2. NOX enzymes are expressed in different tissues and differ in the domains that constitute them, for example, DUOX1 and 2 have an additional peroxidase domain at their N-terminal end [ 16 , 17 ] ( Figure 1 ).…”