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Activation of microglia by endotoxin suppresses the secretion of glial cell line–derived neurotrophic factor (GDNF) through the action of protein kinase Cα (PKCα) and mitogen‐activated protein kinases (MAPKS)
Author(s) -
Matsushita Yuichi,
Nakajima Kazuyuki,
Tohyama Yoko,
Kurihara Tadashi,
Kohsaka Shinichi
Publication year - 2008
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21657
Subject(s) - glial cell line derived neurotrophic factor , microglia , gdnf family of ligands , neurotrophic factors , protein kinase c , secretion , microbiology and biotechnology , kinase , mitogen activated protein kinase , neuroglia , protein kinase a , biology , activator (genetics) , chemistry , endocrinology , receptor , inflammation , immunology , biochemistry , central nervous system
The ability of microglia to produce/secrete glial cell line–derived neurotrophic factor (GDNF) in vitro was examined. Immunoblotting analysis revealed that nonstimulated microglia release limited amounts of GDNF with molecular sizes of 14 and 17 kDa. However, the secreted amounts significantly decreased when the microglia were activated with the endotoxin lipopolysaccharide (LPS). Comparison of the amounts of GDNF in the cells and the conditioned medium between the nonstimulated microglia and LPS‐stimulated microglia clarified that the secretion of GDNF, but not its production, is strongly suppressed when the microglia are activated with LPS. The inhibitor experiments suggested that the GDNF secretion is depressed by a signaling cascade associated with protein kinase C alpha (PKCα) and/or mitogen‐activated protein kinases (MAPKs). As expected from the above results, a PKC activator suppressed the secretion of GDNF in nonstimulated microglia. Taken together, these results demonstrated that microglia have the ability to produce and secrete GDNF in vitro, and that the secretion is suppressed by stimulation with endotoxin, probably due to a signaling mechanism involving PKCα and/or MAPKs. © 2008 Wiley‐Liss, Inc.