Inhaled beta-agonists – drugs that relax constricted airway smooth muscle – are the mainstay of asthma therapy. Some patients, however, do not respond to these drugs.
Previous studies demonstrated that the protein HSP20 is part of the beta-agonist signaling cascade and mediates relaxation of airway smooth muscle. Padmini Komalavilas, Ph.D., and colleagues, have now explored the effects of a cell-permeable peptide (P20) that mimics the action of HSP20.
They demonstrated that P20 relaxed isolated airway smooth muscle and blocked the actions of a contractile drug. In isolated smooth muscle and cultured airway cells, they found that P20 regulated the actin cytoskeleton. They showed that inhaled delivery of P20 reduced airway hyper-responsiveness in vivo in a mouse model of allergic airway disease with features of human asthma.
The results, reported in the American Journal of Respiratory Cell and Molecular Biology, demonstrate that P20 peptide reduces airway hyper-contractility via mechanisms that bypass beta-receptors. The P20 peptide may be a potential therapeutic for asthma that is refractory to beta-agonists.
This research was supported by the National Institutes of Health (grants HL122735, AI111820, AI095227, HL090664, HL122554, AI121420, TR000445) and in part by resources and materials from the Veterans Affairs Tennessee Valley Healthcare System.
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