Mmatory responses including release of pro-inflammatory cytokines and induction of oxidative

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asked Jun 4 in Science by skillrayon0 (290 points)
Our <a href="">SARS-CoV-IN-1 Cancer</a> <a href="">SARS-CoV-IN-1 Anti-infection</a> silica NP preparations showed a relatively low pro-inflammatory activity in vitro and in vivo. Indeed, 5 h after intranasal instillation of 5 mg/kg of SiO2 NP in mice, we did not observe major signs of inflammation in the lungs even when 15  of the cells in BALs <a href="" title=View Abstract(s)">PubMed ID:</a> (mostly macrophages) had internalized those NPs. This is in stark contrast with classical pro-inflammatory molecules like bacterial lipopolysaccharide (LPS). Inhalation of LPS in mice results in acute lung inflammation characterized by <a href="">BCL6-IN-3 Bcl-2 Family</a> elevated <a href="">SARS-CoV-IN-3 Purity & Documentation</a> levels of pro-inflammatory cytokines in BAL fluid as soon as 3 h after administration [23]. When mice BAL fluid were analysed 24 h after NP treatment, a very modest inflammation was induced characterized by a low percentage of neutrophils among BAL cells (less than 10 ) and a slight increase in pro-inflammatory cytokines (Figure 2). Furthermore, incubation ex-vivo of freshly isolated AMs with silica NPs did not induce the release of inflammasome-dependent (IL-1) or -independent cytokines (TNF, KC, IL-6, CCL5, IL-12, IL-10, INF) after 5 h of incubation (data not shown). In contrast to many previous studies our NPs are well characterized, they are not much aggregated and bacterial LPS wasDelaval et al. Particle and Fibre Toxicology (2015) 12:Page 8 ofA)B)7500 5000 2500Neutrophils600000 400000 200000IgM (ng/ml)KC (pg/ml)600 400 200Vehicle/PAKSiO2/PAKVehicle/PAKSiO2/PAKVehicle/PAKSiO2/PAKAlbumin (g/ml)TNF pg/mlIL-6 (pg/ml)4500 3000 15001500 1000 5001000 750 500 250Vehicle/PAKSiO2/PAKVehicle/PAKSiO2/PAKVehicle/PAKSiO2/PAKIL-1 (pg/ml)IL-12 (pg/ml)Vehicle/PAK SiO2/PAKVehicle/PAKSiO2/PAKFigure 8 Effects of silica nanoparticles on inflammatory markers and alveolar-capillar permeability alterations induced by P.a infection. Mice were treated with SiO2 NPs (5 mg/kg;100 g/mice) (open bar) or vehicle (close bar) and 5 h later infected with PAK (2.5x106 CFU/mice). 18 h after infection, number of neutrophils and concentration of cytokines (A), IgM <a href="" title=View Abstract(s)">PubMed ID:</a> and albumin (B) were measured in BALs (2 ml). Basal levels of KC, IL-6 TNF in non-infected mice were 31 ?7, 18 ?4 and 26 ?7 pg/ml (n = 4), respectively (see Figure 2). Basal levels of IL-12 and IL-1 were 50 ?10 pg/ml and not detectable, respectively. Basal levels of IgM in BALs from non-infected mice were 17 ?4 ng/ml (n = 5) (Figure 4). The dotted line in B) represents basal levels of albumin in non-infected mice. Mean ?SEM is represented from 7 to 8 mice per group, *p < 0.05 Mann hitney test.undetectable, probably explaining the very weak inflammatory effect observed. Several studies have described the consequences of NP exposure on immune cells in terms of cellular activation [36,37]. However fewer have focused on the effects of NPs on subsequent anti-microbial host defence mechanisms. We show here that acute exposure to SiO2 NPs increased susceptibility to lethal lung pneumonia induced by P.a.Mmatory responses including release of pro-inflammatory cytokines and induction of oxidative stress [33-35].

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