Fc gamma R/ROS/CK2 alpha Is the Key Inducer of NF-kappa B Activation in a Murine Model of Asthma

Abstract

Background: The transcription factor nuclear factor (NF)-kappa B plays a pivotal role in the development of allergic airway inflammation. However, the mechanism of NF-kappa B activation in asthma remains to be elucidated. Methods: CK2 alpha activation was assessed by CK2 alpha phosphorylation and protein expression. Airway levels of histamine and cytokines were determined by ELISA. We used 2 (active and passive) forms of allergic pulmonary inflammation models. In the active form, the animals were immunized with ovalbumin (OVA) intraperitoneally, followed by an airway challenge with OVA. In the passive form, the animals were passively sensitized by intratracheal instillation with either anti-OVA IgE or anti-OVA IgG, followed by an airway challenge with OVA. The role of NADPH oxidase (NOX) in CK2 alpha activation was assessed using NOX2(-/-) and NOX4(-/-) mice because NOX2 and NOX4 contribute to many inflammatory diseases. Results: The second airway challenge increased CK2 alpha phosphorylation and protein expression in airway epithelial cells as well as nuclear translocation of the p50 and p65 subunits of NF-kappa B, all of which were inhibited by the CK2 alpha inhibitor 4,5,6,7-tetrabromobenzotriazole and the antioxidant N-acetyl-L-cysteine. CK2 alpha phosphorylation and protein expression were significantly impaired in NOX2(-/-), but not in NOX4(-/-), mice. Induction of passive sensitization using anti-OVA IgE activated neither CK2 alpha nor NF-kappa B. In contrast, induction of passive sensitization using anti-OVA IgG activated both CK2 alpha and NF-kappa B. Conclusions: These data suggest that Fc gamma receptor/reactive oxygen species/CK2 alpha is a key inducer of NF-kappa B activation in airway epithelial cells in a murine model of asthma. (c) 2018 S. Karger AG, Basel