Protection from acute lung injury by a peptide designed to inhibit the voltage-gated proton channel
Ruiming Zhao, Benjamin Lopez, Andreas Schwingshackl, Steven A. Goldstein
Abstract
. We now show that intravenous C6 counteracts bacterial lipopolysaccharide (LPS)-induced ALI in mice, and suppresses the accumulation of neutrophils, ROS, and proinflammatory cytokines in bronchoalveolar lavage fluid. Confirming the salutary effects of C6 are via Hv1, genetic deletion of the channel similarly protects mice from LPS-induced ALI. This report reveals that Hv1 is a key regulator of ALI, that Hv1 is a druggable target, and that C6 is a viable agent to treat ALI/ARDS.
Topics & Concepts
ARDSProinflammatory cytokineBronchoalveolar lavageLipopolysaccharideReactive oxygen speciesInflammationNADPH oxidaseMedicinePharmacologyImmunologyAcute respiratory distressRegulatorProteasesLungChemistryBiochemistryInternal medicineEnzymeGeneIon channel regulation and functionNeuroscience of respiration and sleepRespiratory Support and Mechanisms