Effects of Anti-IL-17 on Inflammation, Remodeling, and Oxidative Stress in an Experimental Model of Asthma Exacerbated by LPS

Effects of Anti-IL-17 on Inflammation, Remodeling, and Oxidative Stress in an Experimental Model of Asthma Exacerbated by LPS

Author Camargo, Leandro do Nascimento Google Scholar
Righetti, Renato Fraga Google Scholar
Rolim Barbosa Aristoteles, Luciana Ritha de Cassia Google Scholar
dos Santos, Tabata Maruyama Google Scholar
Ribas de Souza, Flavia Castro Google Scholar
Fukuzaki, Silvia Google Scholar
Cruz, Maysa Mariana Autor UNIFESP Google Scholar
Cardoso Alonso-Vale, Maria Isabel Autor UNIFESP Google Scholar
Mangueira Saraiva-Romanholo, Beatriz Google Scholar
Prado, Carla Maximo Autor UNIFESP Google Scholar
Martins, Milton de Arruda Google Scholar
Leick, Aparecida Google Scholar
Lopes Calvo Tiberio, Iolanda de Fatima Google Scholar
Abstract Inflammation plays a central role in the development of asthma, which is considered an allergic disease with a classic Th2 inflammatory profile. However, cytokine IL-17 has been examined to better understand the pathophysiology of this disease. Severe asthmatic patients experience frequent exacerbations, leading to infection, and subsequently show altered levels of inflammation that are unlikely to be due to the Th2 immune response alone. This study estimates the effects of anti-IL-17 therapy in the pulmonary parenchyma in a murine asthma model exacerbated by LPS. BALB/c mice were sensitized with intraperitoneal ovalbumin and repeatedly exposed to inhalation with ovalbumin, followed by treatment with or without anti-IL-17. Twenty-four hours prior to the end of the 29-day experimental protocol, the two groups received LPS (0.1 mg/ml intratracheal OVA-LPS and OVA-LPS IL-17). We subsequently evaluated bronchoalveolar lavage fluid, performed a lung tissue morphometric analysis, and measured IL-6 gene expression. OVA-LPS-treated animals treated with anti-IL-17 showed decreased pulmonary inflammation, edema, oxidative stress, and extracellular matrix remodeling compared to the non-treated OVA and OVA-LPS groups (p < 0.05). The anti-IL-17 treatment also decreased the numbers of dendritic cells, FOXP3, NF-kappa B, and Rho kinase 1-and 2-positive cells compared to the non-treated OVA and OVA-LPS groups (p < 0.05). In conclusion, these data suggest that inhibition of IL-17 is a promising therapeutic avenue, even in exacerbated asthmatic patients, and significantly contributes to the control of Th1/Th2/Th17 inflammation, chemokine expression, extracellular matrix remodeling, and oxidative stress in a murine experimental asthma model exacerbated by LPS.
Keywords anti-IL-17
distal lung
asthma
inflammation
LPS-exacerbated
xmlui.dri2xhtml.METS-1.0.item-coverage Lausanne
Language English
Sponsor Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
National Council of Scientific and the Technological Development (CNPq)
Laboratory of Medical Investigations
Grant number FAPESP: 2013/17944-1
Laboratory of Medical Investigations: LIM-20 FMUSP
Date 2018
Published in Frontiers In Immunology. Lausanne, v. 8, p. -, 2018.
ISSN 1664-3224 (Sherpa/Romeo, impact factor)
Publisher Frontiers Media Sa
Extent -
Origin http://dx.doi.org/10.3389/fimmu.2017.01835
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000419371800001
URI https://repositorio.unifesp.br/handle/11600/54275

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