Macrophage P2X7 Receptor Function Is Reduced during Schistosomiasis: Putative Role of TGF-β1
Schistosomiasis is a chronic inflammatory disease whose macrophages are involved in immunopathology modulation. Although P2X7 receptor signaling plays an important role in inflammatory responses mediated by macrophages, no reports have examined the role of P2X7 receptors in macrophage function durin...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2014-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2014/134974 |
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| author | Suellen D’arc Santos Oliveira Hayandra Ferreira Nanini Luiz Eduardo Baggio Savio Mariana Caldas Waghabi Claudia Lucia Martins Silva Robson Coutinho-Silva |
| author_facet | Suellen D’arc Santos Oliveira Hayandra Ferreira Nanini Luiz Eduardo Baggio Savio Mariana Caldas Waghabi Claudia Lucia Martins Silva Robson Coutinho-Silva |
| author_sort | Suellen D’arc Santos Oliveira |
| collection | DOAJ |
| description | Schistosomiasis is a chronic inflammatory disease whose macrophages are involved in immunopathology modulation. Although P2X7 receptor signaling plays an important role in inflammatory responses mediated by macrophages, no reports have examined the role of P2X7 receptors in macrophage function during schistosomiasis. Thus, we evaluated P2X7 receptor function in peritoneal macrophages during schistosomiasis using an ATP-induced permeabilization assay and measurements of the intracellular Ca2+ concentration. ATP treatment induced significantly less permeabilization in macrophages from S. mansoni-infected mice than in control cells from uninfected animals. Furthermore, P2X7-mediated increases in intracellular Ca2+ levels were also reduced in macrophages from infected mice. TGF-β1 levels were increased in the peritoneal cavity of infected animals, and pretreatment of control macrophages with TGF-β1 reduced ATP-induced permeabilization, mimicking the effect of S. mansoni infection. Western blot and qRT-PCR data showed no difference in P2X7 protein and mRNA between uninfected, infected, and TGF-β1-treated groups. However, immunofluorescence analysis revealed reduced cell surface localization of P2X7 receptors in macrophages from infected and TGF-β1-treated mice compared to controls. Therefore, our data suggest that schistosomiasis reduces peritoneal macrophage P2X7 receptor signaling. This effect is likely due to the fact that infected mice have increased levels of TGF-β1, which reduces P2X7 receptor cell surface expression. |
| format | Article |
| id | doaj-art-33edd9f28b614914ac7375b42a2a6fc4 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-33edd9f28b614914ac7375b42a2a6fc42025-02-03T06:06:09ZengWileyMediators of Inflammation0962-93511466-18612014-01-01201410.1155/2014/134974134974Macrophage P2X7 Receptor Function Is Reduced during Schistosomiasis: Putative Role of TGF-β1Suellen D’arc Santos Oliveira0Hayandra Ferreira Nanini1Luiz Eduardo Baggio Savio2Mariana Caldas Waghabi3Claudia Lucia Martins Silva4Robson Coutinho-Silva5Laboratory of Immunophysiology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilLaboratory of Immunophysiology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilLaboratory of Immunophysiology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilLaboratory for Functional Genomics and Bioinformatics, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, BrazilLaboratory of Molecular and Biochemical Pharmacology, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, 21941-599 Rio de Janeiro, RJ, BrazilLaboratory of Immunophysiology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilSchistosomiasis is a chronic inflammatory disease whose macrophages are involved in immunopathology modulation. Although P2X7 receptor signaling plays an important role in inflammatory responses mediated by macrophages, no reports have examined the role of P2X7 receptors in macrophage function during schistosomiasis. Thus, we evaluated P2X7 receptor function in peritoneal macrophages during schistosomiasis using an ATP-induced permeabilization assay and measurements of the intracellular Ca2+ concentration. ATP treatment induced significantly less permeabilization in macrophages from S. mansoni-infected mice than in control cells from uninfected animals. Furthermore, P2X7-mediated increases in intracellular Ca2+ levels were also reduced in macrophages from infected mice. TGF-β1 levels were increased in the peritoneal cavity of infected animals, and pretreatment of control macrophages with TGF-β1 reduced ATP-induced permeabilization, mimicking the effect of S. mansoni infection. Western blot and qRT-PCR data showed no difference in P2X7 protein and mRNA between uninfected, infected, and TGF-β1-treated groups. However, immunofluorescence analysis revealed reduced cell surface localization of P2X7 receptors in macrophages from infected and TGF-β1-treated mice compared to controls. Therefore, our data suggest that schistosomiasis reduces peritoneal macrophage P2X7 receptor signaling. This effect is likely due to the fact that infected mice have increased levels of TGF-β1, which reduces P2X7 receptor cell surface expression.http://dx.doi.org/10.1155/2014/134974 |
| spellingShingle | Suellen D’arc Santos Oliveira Hayandra Ferreira Nanini Luiz Eduardo Baggio Savio Mariana Caldas Waghabi Claudia Lucia Martins Silva Robson Coutinho-Silva Macrophage P2X7 Receptor Function Is Reduced during Schistosomiasis: Putative Role of TGF-β1 Mediators of Inflammation |
| title | Macrophage P2X7 Receptor Function Is Reduced during Schistosomiasis: Putative Role of TGF-β1 |
| title_full | Macrophage P2X7 Receptor Function Is Reduced during Schistosomiasis: Putative Role of TGF-β1 |
| title_fullStr | Macrophage P2X7 Receptor Function Is Reduced during Schistosomiasis: Putative Role of TGF-β1 |
| title_full_unstemmed | Macrophage P2X7 Receptor Function Is Reduced during Schistosomiasis: Putative Role of TGF-β1 |
| title_short | Macrophage P2X7 Receptor Function Is Reduced during Schistosomiasis: Putative Role of TGF-β1 |
| title_sort | macrophage p2x7 receptor function is reduced during schistosomiasis putative role of tgf β1 |
| url | http://dx.doi.org/10.1155/2014/134974 |
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