Abstract
There is a well-established association between exposure to air pollutants and pulmonary injuries. For example, metals found in ROFA (residual oil fly ash) increase susceptibility of mice as well as humans to microbial infections. In our research, we have found that vanadate substantially increased the response of several Toll-like receptors (TLRs) to stimulation with their ligands. Although vanadate caused generation of reactive oxygen species (ROS), the addition of ROS scavenger N-acetyl cysteine (NAC) had no effect on augmented lipopolysaccharide (LPS) stimulation. We further showed that vanadate inhibits endosome fusion. This effect was determined by measuring the size of endosomes, NF-κB activity and TLR4 degradation in Hrs (hepatocyte growth factor-regulated tyrosine kinase substrate) overexpressed cells. Moreover, we identified the role of Hrs phosphorylation in these processes. Based on our findings, we can conclude that vanadate potentiates TLR4 activity by increasing Hrs phosphorylation status, reducing the size of Hrs/TLR4-positive endosomes and impacting TLR4 degradation, thus contributing to the detrimental effects of air pollutants on human health.
Highlights
All living organisms are constantly exposed to an external environment filled with microorganisms and air pollutant particles
Most inflammatory effects of residual oil fly ash (ROFA) are attributed to metal ions, vanadium, which is present as a water soluble salt
The augmented NF-kB response to LPS due to the presence of vanadate remained the same regardless of the N-acetyl cysteine (NAC) present (Figure 2D), demonstrating that vanadate-stimulated reactive oxygen species (ROS) production is not responsible for the increased NF-kB responsiveness induced by TLR4 receptor with LPS
Summary
All living organisms are constantly exposed to an external environment filled with microorganisms and air pollutant particles. Epidemiological research has demonstrated a correlation between increased morbidity and mortality of humans and higher concentrations of pollutant particles in ambient air [1]. High concentrations of water soluble metal ions, such as iron, vanadium and nickel are present in ROFA as well [3]. ROFA and particles found in the exhaust dust of diesel fuel (DEP) as well as gases (ozone, SO2, NO2) cause inflammation and damage to the airway [4,5,6,7]. It was proposed that water soluble metal ions (vanadium (V), nickel (II) and iron (III) ions) in ROFA stimulate production of reactive oxygen species (ROS) [8,9,10]. Susceptibility of mice as well as humans to bacterial infections increases upon exposure to ROFA in correlation to its metal content [17,18]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
