2. Academic Validation
  3. POM-1 inhibits P2 receptors and exhibits anti-inflammatory effects in macrophages

POM-1 inhibits P2 receptors and exhibits anti-inflammatory effects in macrophages

  • Purinergic Signal. 2017 Dec;13(4):611-627. doi: 10.1007/s11302-017-9588-x.
Gabriela Pimenta-Dos-Reis 1,  Eduardo José Lopes Torres 2,  Paula Gabriela Quintana 1,  Lincon Onorio Vidal 1,  Bárbara Andréa Fortes Dos Santos 1,  Chuan-Sheng Lin 3 4,  Norton Heise 1,  Pedro Muanis Persechini 1,  Julieta Schachter 5 6
Affiliations

Affiliations

  • 1 Instituto de Biofísica Carlos Chagas Filho da Universidade Federal de Rio de Janeiro, Rio de Janeiro, Brazil.
  • 2 Laboratório de Helmintologia Romero Lascasas Porto, Departamento de Microbiologia, Imunologia e Parasitologia. Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
  • 3 Microbiota Research Center, Chang Gung University, Taoyuan, Taiwan.
  • 4 Center for Molecular and Clinical Immunology, Chang Gung University, Taoyuan, Taiwan.
  • 5 Microbiota Research Center, Chang Gung University, Taoyuan, Taiwan. [email protected].
  • 6 Polo Xerem, Universidade Federal de Rio de Janeiro, Estrada de Xerém No. 27, Xerém, Duque de Caxias, Rio de Janeiro, 25245-390, Brazil. [email protected].
PMID: 29022161 DOI: 10.1007/s11302-017-9588-x
Abstract

Extracellular nucleotides can modulate the immunological response by activating purinergic receptors (P2Rs) on the cell surface of macrophages, dendritic, and other immune cells. In particular, the activation of P2X7R can induce release of cytokines and cell death as well as the uptake of large molecules through the cell membrane by a mechanism still poorly understood. Polyoxotungstate-1 (POM-1) has been proposed as a potent inhibitor of ecto-nucleotidases, enzymes that hydrolyze extracellular nucleotides, regulating the activity of P2Rs. However, the potential impact of POM-1 on P2Rs has not been evaluated. Here, we used Fluorescent Dye uptake, cytoplasmic free Ca2+ concentration measurement, patch-clamp recordings, scanning electron microscopy, and quantification of inflammatory mediators to investigate the effects of POM-1 on P2Rs of murine macrophages. We observed that POM-1 blocks the P2YR-dependent cytoplasmic Ca2+ increase and has partial effects on the cytoplasmic Ca2+, increasing dependence on P2XRs. POM-1 can inhibit the events related with ATP-dependent inflammasome activation, anionic dye uptake, and also the opening of large conductance channels, which are associated with P2X7R-dependent pannexin-1 activation. On the other hand, this compound has no effects on cationic Fluorescent Dye uptake, Apoptosis, and bleb formation, also dependent on P2X7R. Moreover, POM-1 can be considered an anti-inflammatory compound, because it prevents TNF-α and nitric oxide release from LPS-treated macrophages.

Keywords

ATP; Inflammation; Macrophage; POM-1; Purinergic receptor.

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