Inflammasome activation in bovine monocytes by extracellular ATP does not require the purinergic receptor P2X7.
Extracellular adenosine triphosphate (ATP) is a second signal for the assembly of the NLR family, pyrin domain-containing 3 (NLRP3) inflammasome, which form a framework to activate caspase 1, leading to the processing and secretion of the pro-inflammatory cytokine interleukin-1β (IL-1β). The aim of the present study was to investigate the role of the ATP-gated ion channel subtype P2X7 receptor in the inflammasome activation of bovine monocytes. ATP-induced inflammasome assembly in bovine monocytes was shown by caspase-1 activation and the release of IL-1β by LPS/ATP-stimulated bovine cells. The IL-1β release depended on potassium efflux but was independent of reactive oxygen generation of bovine monocytes. Unlike in the human system, a P2X7 receptor antagonist did not block the ATP-induced release of IL-1β of LPS-primed bovine cells. P2X7 mediated pore formation was observed in subsets of bovine T lymphocytes (CD4+>CD8+) but not in monocytes. In addition, ATP and 2-MeSATP but not the high affinity P2X7 agonist BzATP induced calcium influx in bovine monocytes. The data indicate that ROS generation plays no role in the ATP-induced activation of inflammasome in bovine monocytes and that P2X7-mediated pore formation is not necessary for the release of Interleukin-1β.
Institute for Immunology, University of Veterinary Medicine Hannover, Bischofsholer Damm 15, D-30173 Hannover, Germany. jamal.hussen@tiho-hannover.de
Jamal
J
Hussen
Anna
A
Düvel
Mirja
M
Koy
Hans-Joachim
HJ
Schuberth
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002417:Cattle / Q000276:immunology*; D006801:Humans; D058847:Inflammasomes / Q000276:immunology*; D053583:Interleukin-1beta / Q000276:immunology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D058920:Purinergic P2X Receptor Antagonists / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology
D058847:Inflammasomes; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D058920:Purinergic P2X Receptor Antagonists; D017382:Reactive Oxygen Species; D058486:Receptors, Purinergic P2X7; D000255:Adenosine Triphosphate