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

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-κB, 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.

Cigarette and IL-17A synergistically induce bronchial epithelial-mesenchymal transition via activating IL-17R/NF-κB signaling

“…However, our study couldn't conclude that IL-17A could induce EMT in murine bronchial epithelial cells via NF-κB activation, although IL-17A could stimulate IL-17R/NF-κB signaling in those cells. Interestingly, an increase of IL-17A promotes COPD, asthma and lung cancer, which all have a high prrevalence [6,7,22]. And cigarette smoking is widely accepted as a significantly risk factor for those diseases.…”

“…IL-17A is involved in these lung diseases. This interleukin promotes chronic immune inflammation, contributing to occurrence and development of those lung diseases [5][6][7]. In airway, IL-17A could induce production of chemokine and cytokines from bronchial epithelial cells [8,9].…”

Regulatory T‐cells promote pulmonary repair by modulating T helper cell immune responses in lipopolysaccharide‐induced acute respiratory distress syndrome

“…The levels of Th17‐related cytokines, such as IL‐17a, IL‐17f and IL‐22, were markedly increased in the LPS‐induced mouse model of ALI, inducing the pulmonary epithelium to produce chemokines that favour neutrophil infiltration, which is regarded as a proinflammatory mediator and contributor to airway remodelling. 16,17 Blockade of IL‐17 may facilitate pulmonary fibrosis in asthma . However, the relevance of Tregs in the induction of Th17 responses against bacterial infection remains elusive.…”

“…16,17 Blockade of IL-17 may facilitate pulmonary fibrosis in asthma. 39 However, the relevance of Tregs in the induction of Th17 responses against bacterial infection remains elusive. In a murine model of Chlamydia muridarum-induced genital tract infection, Tregs were determined to serve as a prominent inducer of and direct contributor to IL-17/Th17 responses.…”

Severe periodontitis may influence cementum and dental pulp through inflammation, oxidative stress, and apoptosis

“…Inflammation might cause increased local or systemic oxidative stress, due to which, the tissue might experience DNA damage (via oxidation of DNA bases), subsequently inducing tissue apoptosis . Long‐term oxidative stress may also lead to chronic inflammation in non‐communicable diseases, such as cancer and cardiovascular disease .…”