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

Scientific Reports
María Eugenia SchroederMarcelo Hill

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 activators respectively) induced the secretion of IL-1beta. This effect was inhibited by HCQ and also by iberiotoxin and clotrimazol (KCa3.1 inhibitor), arguing against off-target effect. In vitro, HCQ inhibited IL-1beta and caspase 1 activation induced by ATP in a dose-dependent manner. HCQ impaired K+ efflux induced by ATP. In vivo, HCQ inhibited caspase 1-dependent ATP-induced neutrophil recruitment. Our results show that HCQ inhibits Ca++-activated K+ channels. This effect may lea...Continue Reading

References

Jul 1, 1996·The Journal of Membrane Biology·T E DeCourseyF N Quandt
Dec 19, 2003·The New England Journal of Medicine·Mary J RomanJane E Salmon
Aug 9, 2008·The Journal of Clinical Investigation·Kazuyoshi ToyamaHiroto Miura
Sep 17, 2009·Immunological Reviews·Michael D Cahalan, K George Chandy
Apr 16, 2011·American Journal of Respiratory Cell and Molecular Biology·Zhifei ShaoDevendra K Agrawal
Aug 27, 2011·Toxicon : Official Journal of the International Society on Toxinology·Victor ChiK George Chandy
Feb 5, 2014·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Gyorgy PanyiAntonio Felipe
Apr 16, 2014·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·M SegoviaM C Cuturi
May 24, 2014·La Presse médicale·Nathalie Costedoat-ChalumeauGaëlle Guettrot-Imbert
Jul 6, 2014·Current Opinion in Rheumatology·J Michelle Kahlenberg, Mariana J Kaplan
Jul 22, 2014·Nature·Lieselotte Vande WalleMohamed Lamkanfi
Dec 30, 2014·Journal of Cellular Physiology·Kristin FriebelElke Kunisch
Apr 12, 2015·Annual Review of Immunology·Stefan FeskeEdward Y Skolnik
May 31, 2015·Heart Rhythm : the Official Journal of the Heart Rhythm Society·Rebecca A CapelRebecca-Ann B Burton
Feb 26, 2016·Journal of Cellular Physiology·Smriti K RaychaudhuriSiba P Raychaudhuri
May 8, 2016·Cell·Vijay A K Rathinam, Katherine A Fitzgerald

❮ Previous
Next ❯

Citations

Sep 8, 2017·Immunotherapy·Alexis M KalergisPablo A González
Apr 17, 2020·Clinical and Experimental Immunology·M SegoviaM Hill
Nov 30, 2019·Arthritis Research & Therapy·Yuya FujitaKiyoshi Migita
Jul 28, 2020·EMBO Molecular Medicine·Eliise Laura NirkMario Mauthe
Dec 21, 2018·Circulation·Teneema Kuriakose, Thirumala-Devi Kanneganti
Jun 6, 2019·Nature Reviews. Nephrology·Takanori Komada, Daniel A Muruve
Aug 21, 2020·Modern Rheumatology·Kanako NodaHajime Hosoi
Nov 27, 2020·Frontiers in Immunology·Yinhua ZhangZhongji Meng
Feb 26, 2021·Inhalation Toxicology·Rebekah L Kendall, Andrij Holian
Jul 8, 2020·Current Pharmaceutical Design·Gricelis P MartinezMichael R Mijares
Aug 2, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Zhe LiLiqi Bi

❮ Previous
Next ❯

Methods Mentioned

BETA
ELISA
lavage
PMA
ELISAs
FACS

Software Mentioned

Clampfit
Sigmaplot

Related Concepts

Related Feeds

Antimalarial Agents (ASM)

Antimalarial agents, also known as antimalarials, are designed to prevent or cure malaria. Discover the latest research on antimalarial agents here.

Auditory Perception

Auditory perception is the ability to receive and interpret information attained by the ears. Here is the latest research on factors and underlying mechanisms that influence auditory perception.

Antimalarial Agents

Antimalarial agents, also known as antimalarials, are designed to prevent or cure malaria. Discover the latest research on antimalarial agents here.