Cockroach allergen exposure alters redox homeostasis and mediates airway inflammation

Abstract

Allergic diseases are orchestrated by complex interplay of allergens with components of immune system as well as structural cells. As airway epithelium lies at the interface of environment and host immune responses, therefore we sought to study role of cockroach allergen exposure in context of oxidative stress in epithelia and its functional role in allergic pathophysiology. In vitro studies on Beas2B cells indicated elevation of intracellular ROS levels upon cockroach allergen (CE) exposure and transcriptional regulation of epithelial activation markers (CXCL-8 and IL-1 α) and endogenous antioxidant SOD-2. To corroborate ROS induction in vivo, mice model of cockroach hypersensitivity was generated and cytosolic and mitochondrial superoxide levels in lung of mice were estimated along with markers of allergic inflammation (cellular infiltration and epithelial activation cytokines (IL-33, TSLP and IL-25), proinflammatory (Th2 cytokines) and antioxidant pathways. Antioxidant supplementation with NAC, GSH and mitochondria specific ROS scavenger Mito-Tempo significantly reduced allergic inflammation. To discern the role of antioxidant pathways, we examined Nrf2 and SOD2 levels in mice lungs. Our results indicate that cockroach allergen exposure offsets the redox balance in lung with reduced glutathione peroxidase and catalase levels, however antioxidant treatment was able to restore redox equilibrium in lung by upregulating the expression of major regulator of antioxidant signalling, Nrf2 and enzymatic antioxidant SOD2. Our studies indicate crucial role of cockroach allergen induced ROS in allergic pathophysiology and targeting allergen induced oxidative stress may be utilised as an adjunct therapy for allergic diseases.