Calcium and ROS-mediated activation of transcription factors and TNF-α cytokine gene expression in macrophages exposed to ultrafine particles

Abstract

Ultrafine (Uf) particles are a component of particulate air pollution suggested to be responsible for the health effects associated with elevations of this pollutant. We have previously suggested that Uf particles, through the induction of oxidative stress, may induce inflammation in the lung, thus exacerbating preexisting illness in susceptible individuals. Alveolar macrophages are considered to play a key role in particlemediated inflammation and lung disease. The effect of Uf particles on rat alveolar macrophages and human blood monocytes was investigated with reference to the roles of calcium and reactive oxygen species (ROS). TNF-alpha protein release, intracellular calcium concentration, TNF-alpha mRNA expression, and transcription factor activation were studied as end points after treatment of rat alveolar macrophages or peripheral blood monocytes. The calcium channel blocker verapamil, the intracellular calcium chelator BAPTA-AM, the calmodulin inhibitor W-7, and the antioxidants Trolox and Nacystelin (NAL) were included in combination with Uf particles. Verapamil reduced intracellular calcium concentration in rat alveolar macrophages on stimulation with Uf particles. This effect was also apparent with transcription factor AP-1 activation. All antagonists and antioxidants reduced Uf-stimulated nuclear localization of the p50 and p65 subunits of NF-kappaB in human monocytes. Verapamil, BAPTA-AM, and NAL reduced Uf-stimulated TNF-alpha protein release, whereas only verapamil reduced Uf-stimulated mRNA expression in rat alveolar macrophages. In human monocytes, verapamil, Trolox, BAPTA-AM, and W-7 reduced Uf-stimulated TNF-alpha protein release. These findings suggest that Uf particles may exert proinflammatory effects by modulating intracellular calcium concentrations, activation of transcription factors, and cytokine production through a ROS-mediated mechanism.

Effect of Polycyclic Aromatic Hydrocarbons and Carbon Black Particles on Pro-Inflammatory Cytokine Secretion: Impact of PAH Coating Onto Particles

“…CB varied in diameter from 129-592 nm (mean = 260.2 ± 13.7 nm). UfCB had a diameter ranging from 7.7-28.2 nm (mean = 14.3 ± 0.6 nm) (Stone et al, 1998;Brown et al, 2004). Particles were coated with a given PAH as follow: a known amount of adsorbent (CB or ufCB) was placed in a beaker, and the requisite amount of adsorbate (B[a]P, B[b]F, or Pyr, at 10 µg/g particles) was combined in a sufficient amount of dichloromethane such that the particles remained completely submerged.…”

Effects of nano-scale TiO2, ZnO and their bulk counterparts on zebrafish: Acute toxicity, oxidative stress and oxidative damage

“…In suspensions, NPs tend to form large particles and most of the aggregates will settle out of the suspensions in a few hours, which may reduce their toxicities (Adams et al, 2006). On the other hand, reactive oxidative species (ROS) generated through various mechanisms, such as illumination of NPs (Jiang et al, 2008) and disruption of intra-cellular metabolic activities (Long et al, 2006) may disturb the anti-oxidant system (Brown et al, 2004), leading to damage to lipids, carbohydrates, proteins and DNA (Kelly et al, 1998). Previous studies have shown that TiO 2 NPs induced oxidative stress in the brains of rainbow trout (Oncorhynchus mykiss) (Federici et al, 2007).…”

In vitro tagging of embryos with nanoparticles

“…Studies in other cell types have shown that internalized nanoparticles [7] derived from materials other than that tested here disrupted fibroblast and cancer cells after adhering to the cell membranes, impaling and/or releasing toxic ions [27][28][29][30][31][32]. Moreover, nanoparticles internalized into cells increased the reactive oxygen species (ROS), elevated intracellular calcium, activated transcription factors [10] and initiated apoptosis or cell death [14]. Although these events have not been reported for embryos, the possibility exists that specific nanomaterials may interfere with the further development of the blastocysts.…”

“…A nanoparticle or ultrafine particle has a particle mass of less than 100 nm in diameter. Nanoparticles are made from materials such as cadmium selenide [4,5], gold [6], silver [7], perylene [8], polystyrene [9], carbon [10,11], iron oxide [12], silica [13], titanium dioxide [14]. Some types of nanoparticles are organic-based such as latex [15], polylactic acid [16], polyglycolic acid [17] and polyalkylcyanoacrylate [18] while others are based on carbon, sulfates, nitrates [19,20], aluminum, silicon, or titanium [21].…”