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Regulation of microglial activities by glial cell line derived neurotrophic factor
Author(s) -
Chang YuPing,
Fang KuanMing,
Lee TsungI,
Tzeng ShunFen
Publication year - 2005
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.20646
Subject(s) - glial cell line derived neurotrophic factor , gdnf family of ligands , neurotrophic factors , microglia , microbiology and biotechnology , mapk/erk pathway , proinflammatory cytokine , biology , signal transduction , immunology , receptor , inflammation , biochemistry
Much attention has been paid to the ability of glial cell line‐derived neurotrophic factor (GDNF) to protect neurons from neurotoxic insults in the central nervous system (CNS). However, little is known about GDNF action on CNS glia that also can express GDNF receptor systems. In this study, we examined the effects of GDNF on primary rat microglia that function as resident macrophages in the CNS and as the source of proinflammatory mediators upon activation. We found that treatment of primary rat microglia with GDNF had no effect on the secretion of the proinflammatory cytokines, tumor necrosis factor‐α (TNF‐α) and interleukin‐1β (IL‐1β), but it increased the nitric oxide (NO) production to some extent. In addition, GDNF increased the enzymatic activity of superoxide dismutase (SOD), the gene expression of surface antigen intercellular adhesion molecule‐1 (ICAM‐1), the production of the integrin α5 subunit, and the phagocytotic capability in primary rat microglia. Furthermore, inhibition of mitogen‐activated protein kinase (Erk‐MAPK) in the mouse microglial cell line BV2 by U0126 indicated that the MAP kinase signaling pathway may be involved in the regulation of NO and integrin α5 production by GDNF. In vivo evidence also showed that amoeboid cells with integrin α5 or with ED1 immunoreactivity appeared in GDNF‐treated spinal cord tissues at the lesion site 1 week post spinal cord injury (SCI). Furthermore, inhibition of Erk‐MAPK in the mouse microglial cell line BV2 by U0126 indicated that the MAP kinase signaling pathway may be involved in the regulation of NO and integrin α5 production by GDNF. Taken together, our results indicate that GDNF has a positive regulatory effect on microglial activities, such as phagocytosis and the upregulation of adhesion molecules. J. Cell. Biochem. © 2005 Wiley‐Liss, Inc.