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Mediators of Inflammation
Volume 2011 (2011), Article ID 152625, 12 pages
Research Article

Lipopolysaccharide Inhibits the Channel Activity of the P2X7 Receptor

1Centro Fondap de Estudios Moleculares de la Célula Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Chile
2Section on Cellular Signaling, Program on Developmental Neuroscience (PDN), NICHD, Bethesda, Md, USA
3Departamento de Biología, Facultad de Química y Biología y Centro de Biotecnología Acuícola, Universidad de Santiago de Chile (USACH), Chile
4Facultad de Ciencias Biológicas y Facultad de Medicina, Universidad Andrés Bello, Chile
5Instituto de Química, Facultad de Ciencias, Pontificia Universidad Católica de Valparaíso PUCV, Avenida Universidad 330, Curauma, Valparaíso, Chile
6Centro de Regulación Celular y Patología J.V. Luco y Departamento de Fisiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Chile
7Departamento de Ciencias Básicas y Comunitarias, Facultad de Odontología, Universidad de Chile, Chile
8Emory Black, Facultad de Ciencias Médicas, Universidad de Santiago de Chile (USACH), Chile

Received 29 March 2011; Revised 3 June 2011; Accepted 20 June 2011

Academic Editor: Dennis Daniel Taub

Copyright © 2011 Elias Leiva-Salcedo et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.