TNF-α induces the late-phase airway hyperresponsiveness and airway inflammation through cytosolic phospholipase A2 activation

摘要: Background Late-phase airway hyperresponsiveness (AHR) in asthma is considered the event leading to persistent inflammation lungs, but molecular mechanisms involved this process are poorly understood. Objective To examine role of TNF-α development a late AHR and asthma. Methods We established murine model with not only biphasic methacholine also eosinophilia. The effect blockade was determined by using anti–TNF-α antibody knockout mice. Cytosolic phospholipase A 2 (cPLA ) mRNA expression activity were assessed RT-PCR 1-stearoyl-2-[1- 14 C] arachidonyl-sn-glycero-3-phosphocholine as substrate, respectively. Results resulted significant inhibition without affecting early AHR, reduction eosinophilia inflammation. cPLA increased asthmatic lungs TNF-α–dependent way, inhibitor blocked stimulated synthesis metabolites such leukotriene B 4 platelet-activating factor airway. Specific inhibitors inhibited Conclusions proximal key cytokine capable developing late-phase subsequent through expression/activation .