Pro-inflammatory Ca⁺⁺-activated K⁺ channels are inhibited by hydroxychloroquine.

ABSTRACT: Antimalarials have demonstrated beneficial effects in Systemic Lupus Erithematosus and Rheumatoid Arthritis. However, the mechanisms and the molecular players targeted by these drugs remain obscure. Although hydroxychloroquine (HCQ) is a known ion channel inhibitor, this property has not been linked to its anti-inflammatory effects. We aimed to study whether HCQ inhibits pro-inflammatory ion channels. Electrophysiology experiments demonstrated that HCQ inhibited Ca⁺⁺-activated K⁺ conductance in THP-1 macrophages in a dose-dependent manner. In macrophages, ATP-induced K⁺ efflux plays a key role in activating the NLRP3 inflammasome. ATP-induced IL-1beta secretion was controlled by the KCa1.1 inhibitor iberiotoxin. NS1619 and NS309 (KCa1.1 and KCa3.1 activator

SUBMITTER: Eugenia Schroeder M 

PROVIDER: S-EPMC5432501 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature