Requirement for JNK1 in OVA-induced Airway Hyperresponsiveness in vivo

Background Bronchial asthma is a chronic inflammatory disease characterized by airway hyperreactivity (AHR) and inflammatory cell infiltration of the airway. c-Jun N-terminal kinase 1 (JNK1), a member of the mitogen-activated protein kinases, is activated by a variety of stimuli including environmental stress and cytokine(s) and plays a crucial role in the induction of inflammation. To assess the role of JNK1 in the induction of bronchial asthma, we examined the production of AHR, inflammatory reaction, and cytokine production using an ovalbumin (OVA)-induced airway inflammation model. Methods JNK1-deficient (JNK1 -/- ) and control wild-type (WT) mice were primed with intraperitoneal injection of OVA without alum, followed by intranasal administration of OVA. AHR, inflammatory cell accumulation in the airways, and cytokine production were assessed. AHR was also assessed using the irradiated JNK1 -/- and WT mice receiving unprimed WT T plus B cells or cytokine IL13. Finally, IL-4Rα expression on smooth muscle was determined. Results JNK1 -/- mice demonstrated impaired AHR relative to WT mice, while comparable levels of accumulation of inflammatory cells in the airways were seen in JNK1 -/- and WT mice. Although the levels of Th2 cytokine including IL-4 and IL-5 in the OVA-stimulated JNK1 -/- mice were increased relative to the control, JNK1 -/- mice demonstrated a reduced sensitivity to induction of AHR by IL-13, probably due to an impaired increase in IL-4Rα expression on smooth muscle following OVA stimulation. Conclusions