Nitrogen mustard (NM) is a toxic alkylating agent that causes damage to the respiratory tract. indicating inflammation and alveolar-epithelial barrier dysfunction. This was associated with increases in oxidative stress proteins including lipocalin (Lcn)2 and heme oxygenase (HO)-1 in the lung along with pro-inflammatory/cytotoxic (COX-2+ and MMP-9+) and anti-inflammatory/wound repair (CD163+ and Gal-3+) macrophages. Treatment of rats with pentoxifylline (46.7 mg/kg i.p.) daily for 3 d beginning 15 min after NM significantly reduced NM-induced lung XEN445 injury inflammation and oxidative stress as measured histologically and by decreases in BAL cell and protein content and levels of HO-1 and Lcn2. Macrophages expressing COX-2 and MMP-9 also decreased after pentoxifylline while CD163+ and Gal-3+ macrophages increased. This was correlated with persistent upregulation of markers of wound repair including pro-surfactant protein-C and proliferating nuclear cell antigen by Type II cells. NM-induced lung injury and inflammation were associated with alterations in the elastic properties of the lung however these were largely unaltered by pentoxifylline. These data suggest that pentoxifylline may be useful in treating acute lung injury inflammation and oxidative stress induced by vesicants. … Table 1 Effects of pentoxifylline on pulmonary pathology Lcn2 is a member of the lipocalin superfamily known to be up-regulated in response to oxidative stress (Roudkenar et al. 2007 Figure 3 shows that NM administration to rats resulted in an increase in BAL levels of Lcn2 which is consistent with our earlier findings (Sunil et al. 2012 Expression of HO-1 an antioxidant enzyme important in safeguarding the lung from oxidative tension (Ryter et al. 2007 was also improved after NM publicity (Shape 4). This is most prominent in alveolar macrophages. Treatment of rats with pentoxifylline decreased the consequences of NM on macrophage HO-1 manifestation and on BAL Lcn2 amounts (Numbers 3 and ?and44). Shape 3 Ramifications of pentoxifylline on BAL degrees of CCSP and Lcn2. Animals had been treated with PBS or NM accompanied by daily administration of pentoxifylline (PX). After 3 d BAL was collected concentrated and analyzed for CCSP and Lcn2 levels by western blotting. … XEN445 Shape 4 Ramifications of pentoxifylline on NM-induced HO-1 manifestation. Animals had been treated with PBS or NM accompanied by daily administration of pentoxifylline (PX). After 3 d lung sections were stained and prepared with antibody to HO-1. Binding was visualized using … Ramifications of pentoxifylline on NM-induced raises in classically and on the other hand triggered macrophages and on markers XEN445 of cells restoration We previously proven that NM-induced damage can be associated with a build up of classically Rabbit Polyclonal to TNAP1. triggered pro-inflammatory/cytotoxic and on the other hand activated anti-inflammatory/wound restoration macrophages in the lung (Malaviya et al. 2012 In further research the consequences were examined by us of pentoxifylline on NM-induced build up of the macrophage subpopulations. COX-2 can be an inducible enzyme mediating the forming of pro-inflammatory eicosanoids implicated in lung damage and a marker of classically activated macrophages (Laskin et al. 2011 In control rats alveolar macrophages were found to express low levels of COX-2 (Figure 5). A marked increase in COX-2 expression was observed in alveolar macrophages as well as in alveolar epithelial cells following NM exposure. MMP-9 is a matrix metalloproteinase produced by proinflammatory/cytotoxic macrophages and is important in XEN445 tissue injury and remodeling (Muroski et al. 2008 We found that MMP-9 was upregulated in lung macrophages after NM exposure (Figure 5). Pentoxifylline abrogated the effects of NM on both COX-2 and MMP-9 expression in lung macrophages. Figure 5 Effects of pentoxifylline on NM-induced COX-2 and MMP-9 expression. Animals were treated with PBS or NM followed by daily administration of pentoxifylline (PX). After 3 d lung sections were prepared and stained with antibody to COX-2 or MMP-9. Binding … CD163 and Gal-3 are markers of alternatively activated lung macrophages (Gibbons et al. 2011 Gong et al. 2012 MacKinnon et al. 2008 Publicity of animals to NM led to increased amounts of Gal-3+ and CD163+.