Abstract
ATP is an important regulator of microglia and its effects on microglial cytokine release are currently discussed as important contributors in a variety of brain diseases. We here analyzed the effects of ATP on the production of six inflammatory mediators (IL-6, IL-10, CCL2, IFN-γ, TNF-α, and IL-12p70) in cultured mouse primary microglia. Stimulation of P2X7 receptor by ATP (1 mM) or BzATP (500 µM) evoked the mRNA expression and release of proinflammatory cytokines IL-6, TNF-α, and the chemokine CCL2 in WT cells but not in P2X7(-/-) cells. The effects of ATP and BzATP were inhibited by the nonselective P2 receptor antagonists PPADs and suramin. Various selective P2X7 receptor antagonists blocked the P2X7-dependent release of IL-6 and CCL2, but, surprisingly, had no effect on BzATP-induced release of TNF-α in microglia. Calcium measurements confirmed that P2X7 is the main purine receptor activated by BzATP in microglia and showed that all P2X7 antagonists were functional. It is also presented that pannexin-1 hemichannel function and potential P2X4/P2X7 heterodimers are not involved in P2X7-dependent release of IL-6, CCL2, and TNF-α in microglia. How P2X7-specific antagonists only affect P2X7-dependent IL-6 and CCL2 release, but not TNF-α release is at the moment unclear, but indicates that the P2X7-dependent release of cytokines in microglia is differentially regulated.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
