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Treatment of cerebellar granule cell neurons with the neurotrophic factor pigment epithelium‐derived factor in vitro enhances expression of other neurotrophic factors as well as cytokines and chemokines
Author(s) -
Yabe Takeshi,
Herbert J. Taylor,
Takanohashi Asako,
Schwartz Joan P.
Publication year - 2004
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.20196
Subject(s) - pedf , glial cell line derived neurotrophic factor , ciliary neurotrophic factor , neurotrophic factors , microbiology and biotechnology , biology , neurotrophin , nerve growth factor , chemokine , immunology , cancer research , inflammation , receptor , angiogenesis , biochemistry
Microarray analyses demonstrated that a variety of genes was affected by treatment of cerebellar granule cell neurons with the neurotrophic factor pigment epithelium‐derived factor (PEDF). The genes for neurotrophins, glial cell‐derived neurotrophic factor (GDNF), and their receptors were regulated differentially in immature versus mature neurons; however, nerve growth factor (NGF), neurotrophin (NT)‐3, and GDNF did not contribute to the protective effect of PEDF. Brain‐derived neurotrophic factor (BDNF) seemed capable of inducing apoptosis, because a blocking antibody enhanced the protective effect of PEDF. In addition, PEDF exposure also stimulated expression of several cytokine and chemokine genes. Removal of the less than 1% of microglia in the cultures by treatment with L ‐leucine methyl ester, combined with enzyme‐linked immunosorbent assays (ELISAs), demonstrated that the cerebellar granule cells constitutively produce three chemokines, macrophage inflammatory protein (MIP)‐1α, MIP‐2, and MIP‐3α, whose production is enhanced further by treatment with PEDF. Blocking antibodies to each of the chemokines was protective under control conditions, suggesting that they may contribute to the “natural” apoptosis occurring in the cultures, and enhanced the effects of PEDF. Although PEDF enhanced production of all three chemokines, the blocking antibodies did not increase its protective effect against induced apoptosis. These results suggest that although PEDF enhances expression of other neurotrophic factors or chemokines, it does not exert its neuroprotective effect on cerebellar granule cells through their production. © 2004 Wiley‐Liss, Inc.