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P2X4 assembles with P2X7 and pannexin-1 in gingival epithelial cells and modulates reactive oxygen species production and inflammasome activation
PLoS One
  • Shu-Chen Hung, University of California, Merced
  • Chul Hee Choi, University of Florida
  • Najwane Said-Sadier, University of California, Merced
  • Larry Johnson, University of California, Merced
  • Kalina Rosenova Atanasova, University of Florida
  • Hanen Sellami, University of California, San Francisco General Hospital
  • Özlem Yilmaz, University of Florida
  • David M. Ojcius, University of California, San Francisco General Hospital
ORCiD
David M. Ojcius: 0000-0003-1461-4495
Document Type
Article
DOI
10.1371/journal.pone.0070210
Publication Date
7-25-2013
Abstract
We have previously reported that Porphyromonas gingivalis infection of gingival epithelial cells (GEC) requires an exogenous danger signal such as ATP to activate an inflammasome and caspase-1, thereby inducing secretion of interleukin (IL)-1β. Stimulation with extracellular ATP also stimulates production of reactive oxygen species (ROS) in GEC. However, the mechanism by which ROS is generated in response to ATP, and the role that different purinergic receptors may play in inflammasome activation, is still unclear. In this study, we revealed that the purinergic receptor P2X4 is assembled with the receptor P2X7 and its associated pore, pannexin-1. ATP induces ROS production through a complex consisting of the P2X4, P2X7, and pannexin-1. P2X−mediated ROS production can activate the NLRP3 inflammasome and caspase-1. Furthermore, separate depletion or inhibition of P2X4, P2X7, or pannexin-1 complex blocks IL-1β secretion in P. gingivalis-infected GEC following ATP treatment. However, activation via P2X4 alone induces ROS generation but not inflammasome activation. These results suggest that ROS is generated through stimulation of a P2X4/P2X7/pannexin-1 complex, and reveal an unexpected role for P2X4, which acts as a positive regulator of inflammasome activation during microbial infection.
Comments
Article e70210
Citation Information
Shu-Chen Hung, Chul Hee Choi, Najwane Said-Sadier, Larry Johnson, et al.. "P2X4 assembles with P2X7 and pannexin-1 in gingival epithelial cells and modulates reactive oxygen species production and inflammasome activation" PLoS One Vol. 8 Iss. 7 (2013) p. 1 - 12 ISSN: 1932-6203
Available at: http://works.bepress.com/david-ojcius/171/