Bronchial Vascular Remodeling Is Attenuated by Anti-IL-17 in Asthmatic Responses Exacerbated by LPS

Author(s)

Camargo, Leandro do Nascimento ; dos Santos, Tabata Maruyama ; de Andrade, Felipp Costa Pinto ; Fukuzaki, Silvia ; dos Santos Lopes, Fernanda Degobbi Tenorio Quirino ; de Arruda Martins, Milton ; Prado, Carla Maximo ; Leick, Edna Aparecida ; Righetti, Renato Fraga ; Tiberio, Iolanda de Fatima Lopes Calvo

• Document type: Journal article
• Source: FRONTIERS IN PHARMACOLOGY; v. 11, p. 18-pg., 2020-09-04.

Abstract

Introduction Although the major alterations associated with asthma are related to the airways, there is also evidence of the importance of peribronchial vascular inflammation and remodeling in its pathophysiology. Objectives To determine the effects of anti-IL-17 therapy on peribronchial vessels of an asthma model exacerbated by lipopolysaccharide. Methods We evaluated several factors, including lung function, inflammation, oxidative stress, vascular remodeling, and signaling pathways present in the peribronchial vessels of 66 male BALB/c mice exposed to ovalbumin and treated (or not) treated with anti-IL-17. Twenty-four hours before the end of the experimental protocol, groups of sensitized animals (OVA-LPS and OVA-LPS anti-IL-17) also received LPS. Results The OVA-LPS-anti-IL-17 group presented a decrease in several factors [airway resistance and elastance, bronchoalveolar lavage fluid (BALF) cell counts, inflammatory response, eosinophils, TSLP, IL-33, TARC, TNF-alpha, CD4+, CD8+, IL-4, IL-6, IL-10, IL-17, and VEGF positive cells/10(4)mu m(2), peribronchovascular edema, and angiogenesis], including remodeling (MMP-9, MMP-12, TIMP-1 and TGF-beta positive cells and volume fraction of collagen fibers I, collagen fibers III, collagen fibers V, decorin, lumican, actin, biglycan, fibronectin, and integrin), oxidative stress (iNOS positive cells and volume fraction of PGF2 alpha), and signaling pathways (FoxP3), as well as dendritic cells, NF-kB, ROCK-1, ROCK-2, STAT-1, and phosphor-STAT1-positive cells compared to OVA-LPS (p < 0.05). Conclusions In this model of LPS-induced asthma exacerbation, IL-17 inhibition represents a promising therapeutic strategy, indicating the potential of bronchial vascular control of Th2 and Th17 responses and the activation of the remodeling and oxidative stress pathways, associated with the control of signaling pathways. (AU)

• FAPESP's process: 18/02537-5 - Characterization of asthma-COPD overlap syndrome (ACOS): experimental and clinical studies
• Grantee: Iolanda de Fátima Lopes Calvo Tibério
• Support Opportunities: Research Projects - Thematic Grants