| Autor: |
Pimenta-Dos-Reis G; Instituto de Biofísica Carlos Chagas Filho da Universidade Federal de Rio de Janeiro, Rio de Janeiro, Brazil., Torres EJL; 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., Quintana PG; Instituto de Biofísica Carlos Chagas Filho da Universidade Federal de Rio de Janeiro, Rio de Janeiro, Brazil., Vidal LO; Instituto de Biofísica Carlos Chagas Filho da Universidade Federal de Rio de Janeiro, Rio de Janeiro, Brazil., Dos Santos BAF; Instituto de Biofísica Carlos Chagas Filho da Universidade Federal de Rio de Janeiro, Rio de Janeiro, Brazil., Lin CS; Microbiota Research Center, Chang Gung University, Taoyuan, Taiwan.; Center for Molecular and Clinical Immunology, Chang Gung University, Taoyuan, Taiwan., Heise N; Instituto de Biofísica Carlos Chagas Filho da Universidade Federal de Rio de Janeiro, Rio de Janeiro, Brazil., Persechini PM; Instituto de Biofísica Carlos Chagas Filho da Universidade Federal de Rio de Janeiro, Rio de Janeiro, Brazil., Schachter J; Microbiota Research Center, Chang Gung University, Taoyuan, Taiwan. julischachter@gmail.com.; Polo Xerem, Universidade Federal de Rio de Janeiro, Estrada de Xerém No. 27, Xerém, Duque de Caxias, Rio de Janeiro, 25245-390, Brazil. julischachter@gmail.com. |
| Abstrakt: |
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 Ca 2+ 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 Ca 2+ increase and has partial effects on the cytoplasmic Ca 2+ , 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. |
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