Dissociation of FK506-Binding Protein 12.6 kD from Ryanodine Receptor in Bronchial Smooth Muscle Cells in Airway Hyperresponsiveness in Asthma

• DOI: 10.1165/rcmb.2013-0222oc
• Publication Date: 2013-09-20T19:55:51Z
• Authors: Ying Du; Jianhong Zhao; Xi Li; Si Jin; Wan-Li Ma; Qing Mu; Shuxiang Xu; Jie Yang; Shanshan Rao; Liping Zhu; Jianbao Xin; Peng-Cheng Cai; Yunchao Su; Hong Ye
• Keywords: Airway hyperresponsiveness; Bronchial hyperresponsiveness

Airway hyperresponsiveness (AHR) in asthma is predominantly caused by increased sensitivity of bronchial smooth muscle cells (BSMCs) to stimuli. The sarcoplasmic reticulum (SR)-Ca(2+) release channel, known as ryanodine receptor (RyR), mediates the contractive response BSMCs FK506-binding protein 12.6 kD (FKBP12.6) stabilizes RyR2 channel a closed state. However, interaction FKBP12.6 with AHR remains unknown. This study examined asthma. and expression was determined rat model treated inflammatory cytokines. calcium responses contractile agonists were overexpression knockdown FKBP12.6. Asthmatic serum, IL-5, IL-13, TNF-α enhance cause dissociation from decrease gene culture ovalbumin (OVA)-sensitized -challenged rats. Knockdown causes association an increase BSMCs. Overexpression increases RyR2, decreases BSMCs, normalizes airway responsiveness OVA-sensitized Dissociation responsible for contributing Manipulating might be novel useful treatment