RT Journal Article
SR Electronic
T1 The conformational changes of the endoplasmic reticulum-mitochondria unit is involved in the pathogenesis of bronchial asthma
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P857
VO 44
IS Suppl 58
A1 Yong Chul Lee
A1 So Ri Kim
A1 Dong Im Kim
A1 Kyung Bae Lee
YR 2014
UL http://erj.ersjournals.com/content/44/Suppl_58/P857.abstract
AB Under stress conditions, Endoplasmic reticulum (ER) loses the homeostasis in its functions, which is defined as ER stress. ER stress has been suggested to be involved in the inflammatory component of chronic diseases including bronchial asthma. The NLRP3 inflammasome is a molecular platform activated upon signs of cellular 'danger' to trigger innate immune defenses through the maturation of pro-inflammatory cytokines such as IL-1b. Moreover, association between NLRP3 and mitochondria comes from the observation that activated NLRP3 appears to traffic from the ER to perinuclear areas similarly to mitochondria-associated ER membranes (MAMs). In this study, we aimed to investigate whether the allergen-induced cellular stress evokes the conformational association between ER and mitochondria in the airway inflammatory cells and which are involved in the pathogenesis of bronchial asthma. The mice sensitized with OVA and LPS and then challenged with OVA (OVALPS-OVA mice) mice showed the typical features of neutrophilic asthma. Interestingly, confocal analysis and electron-microscopic findings revealed that in BAL cells from OVALPS-OVA mice, the ER and mitochondria get closed each other even seemed to be united one compared to the finding of cells from control mice. An ER stress inhibitor significantly reduced the features of bronchial asthma and the conformational changes of organelles. These findings indicate that the development of ER-mitochondria complex induced by ER stress in airway inflammatory cells may be implicated in the pathogenesis of bronchial asthma, providing the novel therapeutic target for bronchial asthma.