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Polarized Cytokine Release Triggered by P2X7 Receptor from Retinal Pigmented Epithelial Cells Dependent on Calcium Influx.
- Source :
-
Cells [Cells] 2020 Nov 24; Vol. 9 (12). Date of Electronic Publication: 2020 Nov 24. - Publication Year :
- 2020
-
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 Ca <superscript>2+</superscript> and was blocked by Ca <superscript>2+</superscript> chelator BAPTA. IL-6 release and Ca <superscript>2+</superscript> 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 <superscript>-/-</superscript> mouse model of retinal degeneration. In summary, P2X7R stimulation triggers rapid Ca <superscript>2+</superscript> -dependent IL-6 release across the apical membrane of RPE cells.
- Subjects :
- Animals
Cells, Cultured
Disease Models, Animal
Epithelial Cells drug effects
Humans
Inflammasomes metabolism
Interleukin-1beta metabolism
Interleukin-6 metabolism
Mice
Purinergic P2X Receptor Antagonists pharmacology
Retina drug effects
Calcium metabolism
Cytokines metabolism
Epithelial Cells metabolism
Receptors, Purinergic P2X7 metabolism
Retina metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2073-4409
- Volume :
- 9
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Cells
- Publication Type :
- Academic Journal
- Accession number :
- 33255431
- Full Text :
- https://doi.org/10.3390/cells9122537