Lipopolysaccharide Inhibits the Channel Activity of the P2X7 Receptor
The purinergic P2X7 receptor (P2X7R) plays an important role during the immune response, participating in several events such as cytokine release, apoptosis, and necrosis. The bacterial endotoxin lipopolysaccharide (LPS) is one of the strongest stimuli of the immune response, and it has been shown t...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2011-01-01
|
| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2011/152625 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832550281638838272 |
|---|---|
| author | Elias Leiva-Salcedo Claudio Coddou Felipe E. Rodríguez Antonello Penna Ximena Lopez Tanya Neira Ricardo Fernández Mónica Imarai Miguel Rios Jorge Escobar Margarita Montoya J. Pablo Huidobro-Toro Alejandro Escobar Claudio Acuña-Castillo |
| author_facet | Elias Leiva-Salcedo Claudio Coddou Felipe E. Rodríguez Antonello Penna Ximena Lopez Tanya Neira Ricardo Fernández Mónica Imarai Miguel Rios Jorge Escobar Margarita Montoya J. Pablo Huidobro-Toro Alejandro Escobar Claudio Acuña-Castillo |
| author_sort | Elias Leiva-Salcedo |
| collection | DOAJ |
| description | The purinergic P2X7 receptor (P2X7R) plays an important role during the immune response, participating in several events such as cytokine release, apoptosis, and necrosis. The bacterial endotoxin lipopolysaccharide (LPS) is one of the strongest stimuli of the immune response, and it has been shown that P2X7R activation can modulate LPS-induced responses. Moreover, a C-terminal binding site for LPS has been proposed. In order to evaluate if LPS can directly modulate the activity of the P2X7R, we tested several signaling pathways associated with P2X7R activation in HEK293 cells that do not express the TLR-4 receptor. We found that LPS alone was unable to induce any P2X7R-related activity, suggesting that the P2X7R is not directly activated by the endotoxin. On the other hand, preapplication of LPS inhibited ATP-induced currents, intracellular calcium increase, and ethidium bromide uptake and had no effect on ERK activation in HEK293 cells. In splenocytes-derived T-regulatory cells, in which ATP-induced apoptosis is driven by the P2X7R, LPS inhibited ATP-induced apoptosis. Altogether, these results demonstrate that LPS modulates the activity of the P2X7R and suggest that this effect could be of physiological relevance. |
| format | Article |
| id | doaj-art-70ed529568aa4b4d9626a6b70ddc95c5 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2011-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-70ed529568aa4b4d9626a6b70ddc95c52025-02-03T06:07:06ZengWileyMediators of Inflammation0962-93511466-18612011-01-01201110.1155/2011/152625152625Lipopolysaccharide Inhibits the Channel Activity of the P2X7 ReceptorElias Leiva-Salcedo0Claudio Coddou1Felipe E. Rodríguez2Antonello Penna3Ximena Lopez4Tanya Neira5Ricardo Fernández6Mónica Imarai7Miguel Rios8Jorge Escobar9Margarita Montoya10J. Pablo Huidobro-Toro11Alejandro Escobar12Claudio Acuña-Castillo13Centro Fondap de Estudios Moleculares de la Célula Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, ChileSection on Cellular Signaling, Program on Developmental Neuroscience (PDN), NICHD, Bethesda, Md, USADepartamento de Biología, Facultad de Química y Biología y Centro de Biotecnología Acuícola, Universidad de Santiago de Chile (USACH), ChileCentro Fondap de Estudios Moleculares de la Célula Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, ChileDepartamento de Biología, Facultad de Química y Biología y Centro de Biotecnología Acuícola, Universidad de Santiago de Chile (USACH), ChileDepartamento de Biología, Facultad de Química y Biología y Centro de Biotecnología Acuícola, Universidad de Santiago de Chile (USACH), ChileFacultad de Ciencias Biológicas y Facultad de Medicina, Universidad Andrés Bello, ChileDepartamento de Biología, Facultad de Química y Biología y Centro de Biotecnología Acuícola, Universidad de Santiago de Chile (USACH), ChileDepartamento de Biología, Facultad de Química y Biología y Centro de Biotecnología Acuícola, Universidad de Santiago de Chile (USACH), ChileInstituto de Química, Facultad de Ciencias, Pontificia Universidad Católica de Valparaíso PUCV, Avenida Universidad 330, Curauma, Valparaíso, ChileDepartamento de Biología, Facultad de Química y Biología y Centro de Biotecnología Acuícola, Universidad de Santiago de Chile (USACH), ChileCentro de Regulación Celular y Patología J.V. Luco y Departamento de Fisiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, ChileDepartamento de Ciencias Básicas y Comunitarias, Facultad de Odontología, Universidad de Chile, ChileDepartamento de Biología, Facultad de Química y Biología y Centro de Biotecnología Acuícola, Universidad de Santiago de Chile (USACH), ChileThe purinergic P2X7 receptor (P2X7R) plays an important role during the immune response, participating in several events such as cytokine release, apoptosis, and necrosis. The bacterial endotoxin lipopolysaccharide (LPS) is one of the strongest stimuli of the immune response, and it has been shown that P2X7R activation can modulate LPS-induced responses. Moreover, a C-terminal binding site for LPS has been proposed. In order to evaluate if LPS can directly modulate the activity of the P2X7R, we tested several signaling pathways associated with P2X7R activation in HEK293 cells that do not express the TLR-4 receptor. We found that LPS alone was unable to induce any P2X7R-related activity, suggesting that the P2X7R is not directly activated by the endotoxin. On the other hand, preapplication of LPS inhibited ATP-induced currents, intracellular calcium increase, and ethidium bromide uptake and had no effect on ERK activation in HEK293 cells. In splenocytes-derived T-regulatory cells, in which ATP-induced apoptosis is driven by the P2X7R, LPS inhibited ATP-induced apoptosis. Altogether, these results demonstrate that LPS modulates the activity of the P2X7R and suggest that this effect could be of physiological relevance.http://dx.doi.org/10.1155/2011/152625 |
| spellingShingle | Elias Leiva-Salcedo Claudio Coddou Felipe E. Rodríguez Antonello Penna Ximena Lopez Tanya Neira Ricardo Fernández Mónica Imarai Miguel Rios Jorge Escobar Margarita Montoya J. Pablo Huidobro-Toro Alejandro Escobar Claudio Acuña-Castillo Lipopolysaccharide Inhibits the Channel Activity of the P2X7 Receptor Mediators of Inflammation |
| title | Lipopolysaccharide Inhibits the Channel Activity of the P2X7 Receptor |
| title_full | Lipopolysaccharide Inhibits the Channel Activity of the P2X7 Receptor |
| title_fullStr | Lipopolysaccharide Inhibits the Channel Activity of the P2X7 Receptor |
| title_full_unstemmed | Lipopolysaccharide Inhibits the Channel Activity of the P2X7 Receptor |
| title_short | Lipopolysaccharide Inhibits the Channel Activity of the P2X7 Receptor |
| title_sort | lipopolysaccharide inhibits the channel activity of the p2x7 receptor |
| url | http://dx.doi.org/10.1155/2011/152625 |
| work_keys_str_mv | AT eliasleivasalcedo lipopolysaccharideinhibitsthechannelactivityofthep2x7receptor AT claudiocoddou lipopolysaccharideinhibitsthechannelactivityofthep2x7receptor AT felipeerodriguez lipopolysaccharideinhibitsthechannelactivityofthep2x7receptor AT antonellopenna lipopolysaccharideinhibitsthechannelactivityofthep2x7receptor AT ximenalopez lipopolysaccharideinhibitsthechannelactivityofthep2x7receptor AT tanyaneira lipopolysaccharideinhibitsthechannelactivityofthep2x7receptor AT ricardofernandez lipopolysaccharideinhibitsthechannelactivityofthep2x7receptor AT monicaimarai lipopolysaccharideinhibitsthechannelactivityofthep2x7receptor AT miguelrios lipopolysaccharideinhibitsthechannelactivityofthep2x7receptor AT jorgeescobar lipopolysaccharideinhibitsthechannelactivityofthep2x7receptor AT margaritamontoya lipopolysaccharideinhibitsthechannelactivityofthep2x7receptor AT jpablohuidobrotoro lipopolysaccharideinhibitsthechannelactivityofthep2x7receptor AT alejandroescobar lipopolysaccharideinhibitsthechannelactivityofthep2x7receptor AT claudioacunacastillo lipopolysaccharideinhibitsthechannelactivityofthep2x7receptor |