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P2X7‐dependent, but differentially regulated release of IL‐6, CCL2, and TNF‐α in cultured mouse microglia
Author(s) -
Shieh ChuHsin,
Heinrich Annette,
Serchov Tsvetan,
Calker Dietrich,
Biber Knut
Publication year - 2014
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.22628
Subject(s) - microglia , ppads , chemokine , proinflammatory cytokine , biology , tumor necrosis factor alpha , purinergic receptor , receptor , cytokine , microbiology and biotechnology , ccl2 , neuroglia , pharmacology , immunology , inflammation , endocrinology , extracellular , biochemistry , central nervous system
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. GLIA 2014;62:592–607