Requirement of NOX2 and Reactive Oxygen Species for Efficient RIG-I-Mediated Antiviral Response through Regulation of MAVS Expression

The innate immune response is essential to the host defense against viruses, through restriction of virus replication and coordination of the adaptive immune response. Induction of antiviral genes is a tightly regulated process initiated mainly through sensing of invading virus nucleic acids in the cytoplasm by RIG-I like helicases, RIG-I or Mda5, which transmit the signal through a common mitochondria-associated adaptor, MAVS. Although major breakthroughs have recently been made, much remains unknown about the mechanisms that translate virus recognition into antiviral genes expression. Beside the reputed detrimental role, reactive oxygen species (ROS) act as modulators of cellular signaling and gene regulation. NADPH oxidase (NOX) enzymes are a main source of deliberate cellular ROS production. Here, we found that NOX2 and ROS are required for the host cell to trigger an efficient RIG-I-mediated IRF-3 activation and downstream antiviral IFNβ and IFIT1 gene expression. Additionally, we provide evidence that NOX2 is critical for the expression of the central mitochondria-associated adaptor MAVS. Taken together these data reveal a new facet to the regulation of the innate host defense against viruses through the identification of an unrecognized role of NOX2 and ROS

Participation of metallothionein and superoxide dismutase in the blood of smoking smelters

Objectives: Metallothionein (MT) and two forms of superoxide dismutase (SOD), which are dependent on zinc and copper ions, are involved in defense against the same superoxide anion radicals and are present in extra- and intracellular compartments. The aim of our study was to investigate MT concentration and Cu/Zn SOD activity in the plasma and erythrocyte lysate of the non-smoking and smoking smelters. Material and Methods: The investigations were performed in the blood of 300 male smelters and 100 non-exposed male subjects. We have measured zinc, copper, malondialdehyde (MDA) and MT concentrations as well as SOD activity. Results: We have observed an increase of Cu/Zn coefficient and decrease of Zn/Cu coefficient in the serum of smelters in comparison with the non-smoking control group. Concentration of MDA in the plasma of smelters was higher in comparison with its concentration in the non-smoking control group. The plasma and the erythrocyte lysate MT concentration increased significantly in the whole group of smelters as compared to the non-smoking control group. The mean value of MT concentration in plasma of the smoking smelters was above 2-fold higher than in the non-smoking control group. The activity of Cu/Zn SOD in plasma of the smoking and non-smoking smelters was decreased in comparison with the smoking and non-smoking control groups, respectively. The lowest activity of Cu/Zn SOD, about 2-3‑fold decreased in comparison with the smoking and non-smoking control groups, was detected in plasma of the smelters. An inverse relationship was observed in the erythrocyte lysate. The highest activity of Cu/Zn SOD was reported in the erythrocyte lysate of the smoking smelters and it was about 2-fold higher than in the non-smoking control group. Conclusions: In extracellular environment MT plays a crucial role in comparison with the SOD, while in the intracellular compartment Cu/Zn SOD and MT cooperate with each other