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Involvement of purinergic receptors and NOD ‐like receptor‐family protein 3‐inflammasome pathway in the adenosine triphosphate‐induced cytokine release from macrophages
Author(s) -
Gicquel Thomas,
Victoni Tatiana,
Fautrel Alain,
Robert Sacha,
Gleonnec Florence,
Guezingar Marie,
Couillin Isabelle,
Catros Véronique,
Boichot Elisabeth,
Lagente Vincent
Publication year - 2014
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12214
Subject(s) - inflammasome , purinergic receptor , adenosine triphosphate , receptor , pyrin domain , purinergic signalling , microbiology and biotechnology , biology , adenosine receptor , chemistry , biochemistry , agonist
Summary Adenosine triphosphate ( ATP ) has been described as a danger signal activating the NOD ‐like receptor‐family protein 3 ( NLRP 3)‐inflammasome leading to the pro‐inflammatory cytokine, interleukin ( IL )‐1β, release in the lung. The NLRP 3‐inflammasome pathway has been previously described to be involved in experimental collagen deposition and the development of pulmonary fibrosis. The aim of the present study was to investigate the role of the NLRP 3 inflammasome pathway and P2X7 purinergic receptor in the activation of human macrophages in vitro by ATP . We showed that adenosine 5′‐[γ‐thio]triphosphate tetralithium salt ( ATP γS) and 2′,3′‐O‐(4‐benzoylbenzoyl) adenosine 5′‐triphosphate (Bz ATP ), two stable analogs of ATP , are able to potentiate the release of IL ‐1β from human monocyte‐derived macrophages induced by low concentration of lipopolysaccharide ( LPS ). However, in the same conditions no increase in IL ‐1α and IL ‐6 was observed. Immunochemistry has shown that human macrophages natively express NLRP 3 and purinergic P2X 7 receptors (P2X 7 R). NLRP 3 and IL ‐1β m RNA expression were induced from LPS ‐primed macrophages, but also after 5‐h treatment of Bz ATP as analysed by reverse transcription quantitative polymerase chain reaction. However, other inflammasome pathways ( NLRP 1, NLRP 2, NLRC 4, NLRP 6 and AIM 2) and P2X 7 R were not induced by Bz ATP . We observed that P2X 7 R antagonists, A‐438079 and A‐740003, were able to reduce the release of IL ‐1β, but not of IL ‐1α and IL ‐6 from macrophages stimulated by ATP γS or Bz ATP . The present results showed the involvement of the P2X 7 R‐ NLRP 3 inflammasome pathway in the secretion of IL ‐1β from ATP ‐stimulated human macrophages, and suggest that P2X 7 R were not involved in IL ‐1α and IL ‐6 release. This study also points out that repression of the P2X 7 R represents a novel potential therapeutic approach to control fibrosis in lung injury.