Departmental Papers (Dental)
Document Type
Journal Article
Date of this Version
11-24-2020
Publication Source
Cells
Volume
9
Issue
12
DOI
10.3390/cells9122537
Abstract
Cytokine release from non-inflammatory cells is a key step in innate immunity, and agonists triggering cytokine release are central in coordinating responses. P2X7 receptor (P2X7R) stimulation by extracellular ATP is best known to active the NLRP3 inflammasome and release IL-1β, but stimulation also leads to release of other cytokines. As cytokine signaling by retinal pigmented epithelial (RPE) cells is implicated in retinal neurodegeneration, the role of P2X7R in release of cytokine IL-6 from RPE cells was investigated. P2X7R stimulation triggered IL-6 release from primary mouse RPE, human iPS-RPE and human ARPE-19 cells. IL-6 release was polarized, with predominant rise across apical membranes. IL-6 release was inhibited by P2X7R antagonists A438079, A839977, and AZ10606120, but not the NRTI lamivudine (3TC), P2X1R antagonist NF279, or P2Y1R antagonist MRS2179. P2X7R-mediated IL-6 release required extracellular Ca2+ and was blocked by Ca2+ chelator BAPTA. IL-6 release and Ca2+ elevation occurred rapidly, consistent with vesicular IL-6 staining in unstimulated cells. P2X7R stimulation did not trigger IL-1β release in these unprimed cells. P2X7R-mediated IL-6 release was enhanced in RPE cells from the ABCA4-/- mouse model of retinal degeneration. In summary, P2X7R stimulation triggers rapid Ca2+-dependent IL-6 release across the apical membrane of RPE cells.
Keywords
calcium-dependent vesicular release, cytokine release, IL-1β, IL-6, inflammation, innate immunity, P2X7, retina, Animals, Calcium, Cells, Cultured, Cytokines, Disease Models, Animal, Epithelial Cells, Humans, Inflammasomes, Interleukin-1beta, Interleukin-6, Mice, Purinergic P2X Receptor Antagonists, Receptors, Purinergic P2X7, Retina, calcium, cytokine, inflammasome, interleukin 1beta, interleukin 6, purinergic P2X receptor antagonist, purinergic P2X7 receptor, animal, cell culture, disease model, drug effect, epithelium cell, human, metabolism, mouse, retina
Recommended Citation
Shao, X., Guha, S., Lu, W., Campagno, K. E., Beckel, J. M., Mills, J. A., Yang, W., & Mitchell, C. H. (2020). Polarized Cytokine Release Triggered by P2X7 Receptor from Retinal Pigmented Epithelial Cells Dependent on Calcium Influx. Cells, 9 (12), http://dx.doi.org/10.3390/cells9122537
Date Posted: 10 February 2023
This document has been peer reviewed.