Hyperoxia promotes polarization of the immune response in ovalbumin‐induced airway inflammation, leading to a TH₁₇ cell phenotype

Abstract

Previous studies have demonstrated that hyperoxia-induced stress and oxidative damage to the lungs of mice lead to an increase in IL-6, TNF-α, and TGF-β expression. Together, IL-6 and TGF-β have been known to direct T cell differentiation toward the TH17 phenotype. In the current study, we tested the hypothesis that hyperoxia promotes the polarization of T cells to the TH17 cell phenotype in response to ovalbumin-induced acute airway inflammation. Airway inflammation was induced in female BALB/c mice by intraperitoneal sensitization and intranasal introduction of ovalbumin, followed by challenge methacholine. After the methacholine challenge, animals were exposed to hyperoxic conditions in an inhalation chamber for 24 h. The controls were subjected to normoxia or aluminum hydroxide dissolved in phosphate buffered saline. After 24 h of hyperoxia, the number of macrophages and lymphocytes decreased in animals with ovalbumin-induced airway inflammation, whereas the number of neutrophils increased after ovalbumin-induced airway inflammation. The results showed that expression of Nrf2, iNOS, T-bet and IL-17 increased after 24 of hyperoxia in both alveolar macrophages and in lung epithelial cells, compared with both animals that remained in room air, and animals with ovalbumin-induced airway inflammation. Hyperoxia alone without the induction of airway inflammation lead to increased levels of TNF-α and CCL5, whereas hyperoxia after inflammation lead to decreased CCL2 levels. Histological evidence of extravasation of inflammatory cells into the perivascular and peribronchial regions of the lungs was observed after pulmonary inflammation and hyperoxia. Hyperoxia promotes polarization of the immune response toward the TH17 phenotype, resulting in tissue damage associated with oxidative stress, and the migration of neutrophils to the lung and airways. Elucidating the effect of hyperoxia on ovalbumin-induced acute airway inflammation is relevant to preventing or treating asthmatic patients that require oxygen supplementation to reverse the hypoxemia.

Exogenous surfactant prevents hyperoxia-induced lung injury in adult mice

“…This could have important influence on oxidative damage, because neutrophils are a great source of reactive oxygen species [35]. In a previous study, a concomitant elevation of IL-17 levels and neutrophils in the airways induced by hyperoxia were observed [36]. A precursor study showed that hyperoxia-induced inflammatory acute lung injury can be attenuated by inhibition of extracellular HMGB1 [16].…”

The Effects of the Combination of a Refined Carbohydrate Diet and Exposure to Hyperoxia in Mice

“…Clinical hematology is used to evaluate the general state of health of the animal as well as to detect specific diseases [39]. The HG animals had lower serum levels of erythrocytes, hemoglobin, and hematocrit compared to other groups (Table 4).…”

“…The accumulation of H 2 O 2 possible generates, via Fenton and Haber-Weiss reactions, the hydroxyl radical ( ∙ OH) which can react in the side chain and attacks preferably amino acids such as cysteine, histidine, tryptophan, methionine, and phenylalanine, damaging the proteins and, as its consequence, causing the loss of enzyme activity [47]. Diets with high concentrations of lipids and carbohydrates lead to an increase in free fatty acids (FFAs), resulting in an increase of mitochondrial B-oxidation and the overload in the electron transport chain resulting in an increase of production in ROS [39]. Hyperoxia exposes the body to high levels of reactive oxygen species [5, 6] and the high levels of ROS can inhibit the activity of antioxidant enzymes [48].…”

Maternal Tn Immunization Attenuates Hyperoxia-Induced Lung Injury in Neonatal Rats Through Suppression of Oxidative Stress and Inflammation

“…In this study, we used immunohistochemistry to detect the macrophage infiltration on the lung tissue sections. Macrophage phenotype was assessed through immunostaining for iNOS (M1 macrophage marker) and Ym1 (M2 macrophage marker) as hyperoxia increases iNOS expression in macrophages and hyperoxia-exposed murine lungs and inhibits the M2 phenotype in macrophages (39, 40). The rats in the carrier protein + O 2 group significantly exhibited more M1 macrophages than those in the carrier protein + RA or Tn vaccine + RA group.…”