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P2Y12 receptors in primary microglia activate nuclear factor of activated T‐cell signaling to induce C–C chemokine 3 expression
Author(s) -
TozakiSaitoh Hidetoshi,
Miyata Hiroyuki,
Yamashita Tomohiro,
Matsushita Katsuyuki,
Tsuda Makoto,
Inoue Kazuhide
Publication year - 2017
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13968
Subject(s) - microglia , ccl3 , microbiology and biotechnology , p2y12 , purinergic receptor , receptor , biology , chemokine , chemistry , extracellular , inflammation , biochemistry , immunology , platelet , ccl2 , platelet aggregation
Microglia are widely accepted as surveillants in the central nervous system that are continually searching the local environment for signs of injury. Following an inflammatory situation, microglia alter their morphology, extend ramified processes, and undergo cell body hypertrophy. Extracellular nucleotides are recognized as a danger signal by microglia. ADP acting on P2Y12 receptors induce process extension of microglia thereby attracting microglia to the site of adenosine tri‐phosphate/ ADP leaking or release. However, the question whether ADP /P2Y12 receptor signaling directly stimulates the production or release of inducible factors such as cytokines remains unclear. In this study, we found that CC chemokine ligand 3 ( CCL 3) is induced by ADP ‐treated primary microglia. Pharmacological characterization using pertussis toxin, a P2Y12 receptor inhibitor, and a calcium chelator revealed that CCL 3 induction was caused by P2Y12 receptor‐mediated intracellular calcium elevation. Next, nuclear factor of activated T‐cell dephosphorylation and nuclear translocalization were observed. Calcineurin, an inhibitor for nuclear factor of activated T cell, suppressed CCL 3 induction. These data indicate that microglial P2Y12 receptors are utilized to trigger an acute inflammatory response in microglia via rapid CCL 3 induction after ADP stimulation.