Increased airway smooth muscle mass is a key pathology in asthma. Bronchial thermoplasty is a treatment for severe asthma based on selective heating of the airways that aims to reduce the mass of airway smooth muscle cells (ASMC), and thereby bronchoconstriction. However, short heat exposure is insufficient to explain the long-lasting effect and heat shock proteins (HSPs) have been suggested to play a role.
To determine the role of HSP70 and HSP90 in the control of airway wall remodeling by bronchial thermoplasty.
Broncho-alveolar-lavage-fluid and endo-bronchial biopsies of 20 severe asthma patients were obtained before and after thermoplasty. Isolated epithelial cells and ASMC were exposed to 65C for 10 seconds, mimicking thermoplasty. Proteins were determined by immunohistochemistry, Western-blotting, immunofluorescence and ELISA; proliferation by cell counts and Ki67 expression.
Thermoplasty significantly increased the expression of HSP70 and HSP90 in the epithelium and broncho-alveolar-lavage fluid. In ASMC, thermoplasty reduced both HSPs. These cell-type specific effects were detectable even one month after thermoplasty in tissue sections. In epithelial cells, ex vivo exposure to heat (65C, 10 seconds) increased the expression and secretion of HSP70 and HSP90. In addition, epithelial cell proliferation was upregulated by heat or treatment with human recombinant HSP70 or HSP90. In ASMC, heat exposure or exogenous HSPs reduced proliferation and differentiation. In both cell types, HSP70 and HSP90 activated the signaling cascade of AKT→mTOR→p70S6K and C/EBP-β→PRMT1→ mitochondria activity.
Epithelial cell-derived HSP70 and HSP90 improve the function of epithelial cells, but block ASMC remodeling.
The beneficial effect of bronchial thermoplasty on the airway structure might be explained by the lasting activation of bronchial epithelial cells and increased secretion of HSP70 and HSP90.

Copyright © 2021. Published by Elsevier Inc.