Extracellular ATP acting at the P2X7 receptor inhibits secretion of soluble HLA-G from human monocytes.
Roberta Rizzo,Davide Ferrari,Loredana Melchiorri,Marina Stignani,Sara Gulinelli,Olavio R. Baricordi,Francesco Di Virgilio +6 more
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TLDR
It is shown that extracellular ATP impairs in an IL-10-dependent fashion the expression of the tolerogenic soluble and membrane-bound HLA-G Ag in human monocytes, pointing to a specific role of the P2X7 receptor.Abstract:
Bacterial LPS induces the release of ATP from immune cells. Accruing evidence suggests that extracellular ATP participates in the inflammatory response as a proinflammatory mediator by activating the inflammasome complex, inducing secretion of cytokines (IL-1, IL-18) and cell damaging agents such as oxygen radicals, cationic proteins, and metalloproteases. It is not known whether ATP can also act as a proinflammatory mediator by inhibiting production of molecules down-modulating the immune response. Here, we show that extracellular ATP impairs in an IL-10-dependent fashion the expression of the tolerogenic soluble and membrane-bound HLA-G Ag in human monocytes. The effect of ATP was mimicked by BzATP (3'-O-(4-benzoyl)benzoyl-ATP) and greatly reduced by pretreatment with oATP (periodate-oxidized ATP), KN-62 (1-[N,O-bis(5-isoquinoline-sulfonyl)-N-methyl-l-tyrosyl]-4-phenylpiperazine), and an anti-P2X(7) mAb, thus pointing to a specific role of the P2X(7) receptor. The effect of ATP was time- and dose-dependent and was not due to a decrease in expression of IL-10 receptor. Inhibition by ATP was reverted by supplementation of culture medium with exogenous IL-10. Due to the well-known immunosuppressive activity of IL-10 and soluble HLA-G, this novel effect of ATP might be relevant for the pathophysiology and therapy of inflammatory disorders.read more
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The P2X7 Receptor in Infection and Inflammation
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P2X7 in Cancer: From Molecular Mechanisms to Therapeutics.
Romain Lara,Elena Adinolfi,Catherine A. Harwood,Michael P. Philpott,Julian A. Barden,Francesco Di Virgilio,Shaun McNulty +6 more
TL;DR: Significantly, the effects of both P2X7 agonists and antagonists in preclinical tumor models of cancer demonstrate the potential for agents modifying P2x7 function, to provide innovative cancer therapies.
References
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TL;DR: Molecules involved in TLR4-mediated signaling are reviewed, including players that are involved in the negative regulation of this important pathway.
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Susan Kovats,Elliott K. Main,Clifford Librach,Marcia Stubblebine,Susan J. Fisher,Robert DeMars +5 more
TL;DR: HLA-G is subject to both cell type-specific and developmental regulation and is expressed in early gestation human cytotrophoblasts and is present in choriocarcinoma cell lines studied.
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The P2Y12 receptor regulates microglial activation by extracellular nucleotides
Sharon E Haynes,Gunther Hollopeter,Gunther Hollopeter,Guang Yang,Dana Kurpius,Michael E. Dailey,Wen-Biao Gan,David Julius +7 more
TL;DR: It is shown that microglia from mice lacking Gi-coupled P2Y12 receptors exhibit normal baseline motility but are unable to polarize, migrate or extend processes toward nucleotides in vitro or in vivo, implying that P2 Y12 is a primary site at which nucleotide act to induce microglial chemotaxis at early stages of the response to local CNS injury.
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Adenosine 5'-triphosphate and adenosine as endogenous signaling molecules in immunity and inflammation
TL;DR: The overwhelming evidence indicates that ATP and Ado are important endogenous signaling molecules in immunity and inflammation, and it is proposed that their immunological role is both interdependent and multifaceted, meaning that the nature of their effects may shift from immunostimulatory to immunoregulatory or vice versa depending on extracellular concentrations as well as on expression patterns of purinergic receptors and ecto-enzymes.
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