title: Lipopolysaccharide inhibits the channel activity of the P2X7 receptor.
abstract: 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.
authors.affiliation: Centro Fondap de Estudios Moleculares de la Célula Instituto de Ciencias Biomédicas, Universidad de Chile.
authors.forename: Elias
authors.initials: E
authors.lastname: Leiva-Salcedo
authors.forename: Claudio
authors.initials: C
authors.lastname: Coddou
authors.forename: Felipe E
authors.initials: FE
authors.lastname: Rodríguez
authors.forename: Antonello
authors.initials: A
authors.lastname: Penna
authors.forename: Ximena
authors.initials: X
authors.lastname: Lopez
authors.forename: Tanya
authors.initials: T
authors.lastname: Neira
authors.forename: Ricardo
authors.initials: R
authors.lastname: Fernández
authors.forename: Mónica
authors.initials: M
authors.lastname: Imarai
authors.forename: Miguel
authors.initials: M
authors.lastname: Rios
authors.forename: Jorge
authors.initials: J
authors.lastname: Escobar
authors.forename: Margarita
authors.initials: M
authors.lastname: Montoya
authors.forename: J Pablo
authors.initials: JP
authors.lastname: Huidobro-Toro
authors.forename: Alejandro
authors.initials: A
authors.lastname: Escobar
authors.forename: Claudio
authors.initials: C
authors.lastname: Acuña-Castillo
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D057809:HEK293 Cells / Q000187:drug effects; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018408:Patch-Clamp Techniques; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D008070:Lipopolysaccharides; D058486:Receptors, Purinergic P2X7; D000255:Adenosine Triphosphate; D048049:Extracellular Signal-Regulated MAP Kinases; D002118:Calcium