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Fas-associated factor 1 is a death-promoting protein that induces apoptosis by interacting with the Fas receptor. Until now, FAF1 was reported to interact potentially with diverse proteins and to function as a negative and/or positive regulator of several cellular possesses. However, the role of FAF1 in defense against bacterial infection remains unclear. Here, we show that FAF1 plays a pivotal role in activating NADPH oxidase in macrophages during Listeria monocytogenes infection. Upon infection by L. monocytogenes, FAF1 interacts with p67phox (an activator of the NADPH oxidase complex), thereby facilitating its stabilization and increasing the activity of NADPH oxidase. Consequently, knockdown or ectopic expression of FAF1 had a marked effect on production of ROS, proinflammatory cytokines, and antibacterial activity, in macrophages upon stimulation of TLR2 or after infection with L. monocytogenes. Consistent with this, FAF1gt/gt mice, which are knocked down in FAF1, showed weaker inflammatory responses than wild-type mice; these weaker responses led to increased replication of L. monocytogenes. Collectively, these findings suggest that FAF1 positively regulates NADPH oxidase-mediated ROS production and antibacterial defenses.
This article was published in the following journal.
Name: PLoS pathogens
The activation of NADPH oxidase contributes to dopaminergic neurodegeneration and motor deficits in Parkinson's disease (PD). However, whether NADPH oxidase is involved in non-motor symptoms, especial...
NADPH oxidase (Nox) -derived reactive oxygen species have been implicated in redox signaling via cysteine oxidation in target proteins. Although the importance of oxidation of target proteins is well ...
Endothelial progenitor cells (EPCs) may contribute to ischemia-induced angiogenesis in atherosclerotic diseases. The protein kinase C (PKC) family is involved in the regulation of angiogenesis, howeve...
The activation of NADPH oxidase contributes to dopaminergic neurodegeneration induced by paraquat and maneb, two concurrently used pesticides in agriculture. However, the mechanisms remain unclear. Fe...
Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and oxidative stress is usually considered as an important factor to the pathogenesis of various diseases. Inorganic nitrite, previously vie...
Obstructive Sleep Apnea (OSA) is associated with increased oxidative stress. The major sources of Reactive Oxygen Species (ROS) in the vasculature are the NADPH oxidases. Several polymorph...
A placebo-controlled, multicenter, randomized trial to test GKT137831 in ambulatory patients with idiopathic pulmonary fibrosis. This drug is an inhibitor of nicotinamide adenine dinucleot...
Our recent data in mice have demonstrated a key role of xanthine oxidase in hyperglycemia-induced by Reactive oxygen species production, and a preventive role of allopurinol (inhibitor of ...
X-linked chronic granulomatous disease (X-CGD) is a rare genetic disorder, which affects boys. It is a primary immunodeficiency disorder which results from an inability of the white blood ...
The overall objective of this clinical study is to determine if smokers who switch from their usual high reactive oxygen and nitrous oxide species (ROS/NOS) products to a low ROS/NOS produ...
An NADPH oxidase that is expressed by PHAGOCYTES where it transfers electrons across the plasma membrane from cytosolic NADPH to molecular oxygen on the exterior. It regulates proton (H+) flux into resting phagocytes to control intracellular pH. Mutations in the CYBB gene are associated with X-LINKED CHRONIC GRANULOMATOUS DISEASE.
A flavoprotein enzyme that catalyzes the univalent reduction of OXYGEN using NADPH as an electron donor to create SUPEROXIDE ANION. The enzyme is dependent on a variety of CYTOCHROMES. Defects in the production of superoxide ions by enzymes such as NADPH oxidase result in GRANULOMATOUS DISEASE, CHRONIC.
A large increase in oxygen uptake by neutrophils and most types of tissue macrophages through activation of an NADPH-cytochrome b-dependent oxidase that reduces oxygen to a superoxide. Individuals with an inherited defect in which the oxidase that reduces oxygen to superoxide is decreased or absent (GRANULOMATOUS DISEASE, CHRONIC) often die as a result of recurrent bacterial infections.
A mixed function oxidase enzyme which during hemoglobin catabolism catalyzes the degradation of heme to ferrous iron, carbon monoxide and biliverdin in the presence of molecular oxygen and reduced NADPH. The enzyme is induced by metals, particularly cobalt. EC 188.8.131.52.
An NADPH oxidase that functions as a voltage-gated proton channel expressed by PHAGOCYTES, especially in the colon. It regulates intracellular pH, generates SUPEROXIDES upon activation by PHAGOCYTOSIS, and may play a role in INNATE IMMUNITY.
Antiretroviral Therapy Clostridium Difficile Ebola HIV & AIDS Infectious Diseases Influenza Malaria Measles Sepsis Swine Flu Tropical Medicine Tuberculosis Infectious diseases are caused by pathogenic...