TLR2/MyD88/NF-κB Pathway, Reactive Oxygen Species, Potassium Efflux Activates NLRP3/ASC Inflammasome during Respiratory Syncytial Virus Infection

Human respiratory syncytial virus (RSV) constitute highly pathogenic virus that cause severe respiratory diseases in newborn, children, elderly and immuno-compromised individuals. Airway inflammation is a critical regulator of disease outcome in RSV infected hosts. Although “controlled” inflammation is required for virus clearance, aberrant and exaggerated inflammation during RSV infection results in development of inflammatory diseases like pneumonia and bronchiolitis. Interleukin-1β (IL-1β) plays an important role in inflammation by orchestrating the pro-inflammatory response. IL-1β is synthesized as an immature pro-IL-1β form. It is cleaved by activated caspase-1 to yield mature IL-1β that is secreted extracellularly. Activation of caspase-1 is mediated by a multi-protein complex known as the inflammasome. Although RSV infection results in IL-1β release, the mechanism is unknown. Here in, we have characterized the mechanism of IL-1β secretion following RSV infection. Our study revealed that NLRP3/ASC inflammasome activation is crucial for IL-1β production during RSV infection. Further studies illustrated that prior to inflammasome formation; the “first signal” constitutes activation of toll-like receptor-2 (TLR2)/MyD88/NF-κB pathway. TLR2/MyD88/NF-κB signaling is required for pro-IL-1β and NLRP3 gene expression during RSV infection. Following expression of these genes, two “second signals” are essential for triggering inflammasome activation. Intracellular reactive oxygen species (ROS) and potassium (K+) efflux due to stimulation of ATP-sensitive ion channel promote inflammasome activation following RSV infection. Thus, our studies have underscored the requirement of TLR2/MyD88/NF-κB pathway (first signal) and ROS/potassium efflux (second signal) for NLRP3/ASC inflammasome formation, leading to caspase-1 activation and subsequent IL-1β release during RSV infection

Thermal and mechanical properties of modified CaCO3 filled poly (ethylene terephthalate) nanocomposites

Poly(ethylene terephthalate) (PET)/CaCO3 and PET/modified-CaCO3 (m-CaCO3) nanocomposites were prepared by melt blending. The morphology indicated that m-CaCO3 produced by reacting sodium oxalate and calcium chloride, was well dispersed in PET matrix and showed good interfacial interaction with PET compared to CaCO3. No significant differences in the thermal properties such as, glass transition, melting and degradation temperatures, of the nanocomposites were observed. The thermal shrinkage of PET at 120 ??C was 10.8 %, while those of PET/CaCO3 and PET/m-CaCO3 nanocomposites were 2.9-5.2 % and 1.2-2.8 %, respectively depending on filler content. The tensile strength of PET/CaCO3 nanocomposite decreased with CaCO3 loading, whereas that of PET/m-CaCO3 nanocomposites at 0.5 wt% loading showed a 17 % improvement as compared to neat PET. The storage modulus at 120 ??C increased from 1660 MPa for PET to 2350 MPa for PET/CaCO3 nanocomposite at 3 wt% loading, and 3230 MPa for PET/m-CaCO3 nanocomposite at 1 wt% loadinclose0

Reactive oxygen and nitrogen species during viral infections

Abstract Oxygen and nitrogen radicals are frequently produced during viral infections. These radicals are not only a physiological mechanism for pathogen clearance but also result in many pathological consequences. Low concentrations of radicals can promote viral replication; however high concentrations of radicals can also inhibit viral replication and are detrimental to the cell due to their mitogenic activity. We reviewed the detailed mechanisms behind oxygen and nitrogen radical production and focused on how viruses induce radical production. In addition, we examined the effects of oxygen and nitrogen radicals on both the virus and host. We also reviewed enzymatic and chemical detoxification mechanisms and recent advances in therapeutic antioxidant applications. Many molecules that modulate the redox balance have yielded promising results in cell and animal models of infection. This encourages their use in clinical practice either alone or with existing therapies. However, since the redox balance also plays an important role in host defence against pathogens, carefully designed clinical trials are needed to assess the therapeutic benefits and secondary effects of these molecules and whether these effects differ between different types of viral infections