Righetti Renato Fraga, Dos Santos Tabata Maruyama, Camargo Leandro do Nascimento, Aristóteles Luciana Ritha Cássia Rolim Barbosa, Fukuzaki Silvia, de Souza Flávia Castro Ribas, Santana Fernanda Paula Roncon, de Agrela Marcus Vinicius Rodrigues, Cruz Maysa Mariana, Alonso-Vale Maria Isabel Cardoso, Genaro Isabella Santos, Saraiva-Romanholo Beatriz Mangueira, Leick Edna Aparecida, Martins Milton de Arruda, Prado Carla Máximo, Tibério Iolanda de Fátima Lopes Calvo
Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo, Brazil.
Hospital Sírio-Libanês, São Paulo, Brazil.
Front Pharmacol. 2018 Oct 4;9:1021. doi: 10.3389/fphar.2018.01021. eCollection 2018.
T helper 17 (Th17) has been implicated in a variety of inflammatory lung and immune system diseases. However, little is known about the expression and biological role of IL-17 in acute lung injury (ALI). We investigated the mechanisms involved in the effect of anti-IL17 in a model of lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. Mice were pre-treated with anti-IL17, 1h before saline/LPS intratracheal administration alongside non-treated controls and levels of exhaled nitric oxide (eNO), cytokine expression, extracellular matrix remodeling and oxidative stress, as well as immune cell counts in bronchoalveolar lavage fluid (BALF), and respiratory mechanics were assessed in lung tissue. LPS instillation led to an increase in multiple cytokines, proteases, nuclear factor-κB, and Forkhead box P3 (FOXP3), eNO and regulators of the actomyosin cytoskeleton, the number of CD4+ and iNOS-positive cells as well as the number of neutrophils and macrophages in BALF, resistance and elastance of the respiratory system, ARG-1 gene expression, collagen fibers, and actin and 8-iso-PGF2α volume fractions. Pre-treatment with anti-IL17 led to a significant reduction in the level of all assessed factors. Anti-IL17 can protect the lungs from the inflammatory effects of LPS-induced ALI, primarily mediated by the reduced expression of cytokines and oxidative stress. This suggests that further studies using anti-IL17 in a treatment regime would be highly worthwhile.
辅助性T细胞17（Th17）与多种肺部炎症和免疫系统疾病有关。然而，关于白细胞介素-17（IL-17）在急性肺损伤（ALI）中的表达和生物学作用知之甚少。我们在脂多糖（LPS）诱导的小鼠急性肺损伤（ALI）模型中研究了抗IL-17作用的相关机制。在气管内给予生理盐水/LPS前1小时，用抗IL-17对小鼠进行预处理，同时设置未处理的对照组，评估呼出一氧化氮（eNO）水平、细胞因子表达、细胞外基质重塑和氧化应激，以及支气管肺泡灌洗液（BALF）中的免疫细胞计数，并测定肺组织的呼吸力学。LPS滴注导致多种细胞因子、蛋白酶、核因子-κB和叉头框P3（FOXP3）、eNO以及肌动球蛋白细胞骨架调节因子增加，BALF中CD4+和诱导型一氧化氮合酶（iNOS）阳性细胞数量以及中性粒细胞和巨噬细胞数量增加，呼吸系统的阻力和弹性增加，精氨酸酶-1（ARG-1）基因表达、胶原纤维以及肌动蛋白和8-异前列腺素F2α体积分数增加。用抗IL-17预处理可导致所有评估因子水平显著降低。抗IL-17可保护肺部免受LPS诱导的ALI的炎症影响，主要是通过细胞因子表达降低和氧化应激介导的。这表明在治疗方案中使用抗IL-17进行进一步研究将非常有价值。
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