[HSP90α exacerbates house dust mite-induced asthmatic airway inflammation by upregulating endoplasmic reticulum stress in bronchial epithelial cells].

Objective: To explore the role of heat shock protein 90α (HSP90α) and endoplasmic reticulum (ER) stress pathway in allergic airway inflammation induced by house dust mite (HDM) in bronchial epithelial cells.

Methods: A HDM- induced asthmatic cell model was established in human bronchial epithelial (HBE) cells by exposure to a concentration gradient (200, 400 and 800 U/mL) of HDM for 24 h. To test the effect of siHSP90α and HSP90 inhibitor 17-AAG on HDM-induced asthmatic inflammation, HBE cells were transfected with siHSP90α (50 nmol, 12 h) or pretreated with 17-AAG (900 nmol, 6 h) prior to HDM exposure (800 U/mL) for 24 h, and the changes in the expression of HSP90α and ER stress markers were assessed. We also tested the effect of nasal drip of 17-AAG, HDM, or their combination on airway inflammation and ER stress in C57BL/6 mice.

Results: In HBE cells, HDM exposure significantly up-regulated the expression of HSP90α protein (=0.011) and ER stress markers XBP-1 (=0.044), ATF-6α (=0.030) and GRP-78 (=0.027). Knocking down HSP90α and treatment with 17-AAG both significantly inhibited HDM-induced upregulation of XBP-1 (=0.008). In C57BL/6 mice, treatment with 17-AAG obviously improved HDM-induced airway inflammation and significantly reduced the number of inflammatory cells in the airway (=0.014) and lowered the levels of IL-4 (=0.030) and IL-5 (=0.035) in alveolar lavage fluid. Immunohistochemical staining showed that the expressions of XBP-1 and GRP-78 in airway epithelial cells decreased significantly after the treatment of 17-AAG.

Conclusions: HSP90α promotes HDM-induced airway allergic inflammation possibly by upregulating ER stress pathway in bronchial epithelial cells.