Background and aims: Expansion and morphological dysregulation of the bronchial vascular network occurs in asthmatic airways. Interleukin (IL) -17 and Rho-kinase (ROCK) are known to act in inflammation control and remodeling. Modulation of Rho-kinase proteins and IL-17 may be a promising approach for the treatment of asthma through the control of angiogenesis. Our objective was to analyze the effects of treatment with anti-IL17 and/or Rho-kinase inhibitor on vascular changes in mice with chronic allergic pulmonary inflammation. Methods: Sixty-four BALB/c mice, with pulmonary inflammation induced by ovalbumin were treated with anti-IL17A (7.5/µg per dose, intraperitoneal) and/or Rho-kinase inhibitor (Y-27632-10 mg/kg, intranasal), 1 h before each ovalbumin challenge (22, 24, 26, and 28/days). Control animals were made to inhale saline. At the end of the protocol, lungs were removed, and morphometric analysis was performed to quantify vascular inflammatory, remodeling, and oxidative stress responses. Results: Anti-IL17 or Rho-kinase inhibitor reduced the number of CD4+, CD8+, dendritic cells, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17, Rho-kinase 1 and 2, transforming growth factor (TGF-β), vascular endothelial growth factor (VEGF), nuclear factor (NF)-KappaB, iNOS, metalloproteinase (MMP)-9, MMP-12, metalloproteinase inhibitor-1 (TIMP-1), FOXP-3, signal transducer and activator of transcription 1 (STAT1) and phospho-STAT1-positive cells, and actin, endothelin-1, isoprostane, biglycan, decorin, fibronectin and the collagen fibers volume fraction compared with the ovalbumin group ( p < 0.05). The combination treatment, when compared with anti-IL17, resulted in potentiation of decrease in the number of IL1β- and dendritic cells-positive cells. When we compared the OVA-RHO inhibitor-anti-IL17 with OVA-RHO inhibitor we found a reduction in the number of CD8+ and IL-17, TGF-β, and phospho-STAT1-positive cells and endothelin-1 in the vessels ( p < 0.05). There was an attenuation in the number of ROCK 2-positive cells in the group with the combined treatment when compared with anti-IL17 or Rho-kinase inhibitor-treated groups ( p < 0.05). Conclusion: We observed no difference in angiogenesis after treatment with Rho-kinase inhibitor and anti-IL17. Although the treatments did not show differences in angiogenesis, they showed differences in the markers involved in the angiogenesis process contributing to inflammation control and vascular remodeling. The reviews of this paper are available via the supplemental material section.

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Background: Prolonged exposure to iron powder and other mineral dusts can harm affected populations, especially those with COPD. The goal of this study was to see how environmental exposure to metal dust affected lung mechanics, inflammation, remodeling, oxidative stress responses, and elastase in mice in two different mining centers in Vitória, ES, Brazil. Methods: This study utilized 72 male C57Bl/6 mice (36 summer and 36 winter), which were divided into six groups: control, non-exposed (SAL); non-exposed, given elastase (ELA); exposed to metal powder at a mining company (SAL-L1 and ELA-L1); and exposed to a location three miles away from the mining company (SAL-L2 and ELA-L2) for four weeks. On the 29th day of the protocol, the researchers assessed lung mechanics, bronchoalveolar lavage fluid (BALF), inflammation, remodeling, oxidative stress, and alveolar wall alterations (mean linear intercept – Lm). Results: ELA, ELA-L1 and ELA-L2 had an increase in Lm compared to the SAL groups (p<0.05). There was an increase in total cells and macrophages in ELA-L1 and ELA-L2 compared to the other groups (p<0.05). Exposed groups (ELA-L1, ELA-L2, SAL-L1, and SAL-L2) had an increase in cell expression of Inflammatory markers (IL-1β, IL-6, IL-10, IL-17, TNF-α, and neutrophils) (p<0.05); remodeling markers (TIMP-1, MMP-9, MMP-12, TGF-β, collagen fibers and MUC5AC); oxidative stress (iNOS); and mechanisms involved (NFkB) increased compared to ELA and SAL (p<0.05). Although we did not find differences in lung mechanics across all groups, there were low to moderate correlations between these parameters (elastance and resistance of lung tissue) (p0.05). Conclusions: Aside from lung mechanics, environmental exposure to iron and metal powder exacerbated inflammation, remodeling, and oxidative stress responses in exposed mice with and without emphysema. The mechanisms involved are dependent on iNOS and NFkB activation.

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