Regulation of GDNF expression in cultured astrocytes by inflammatory stimuli.
Astrocytes express increased levels of neurotrophic factors in response to pathological conditions in the CNS such as injury and inflammation. We have examined the effects of lipopolysaccharide (LPS) and inflammatory cytokines on the expression of GDNF by mouse astrocytes and by C6 glial cells. LPS and tumor necrosis factor-alpha (TNF-alpha) induced an increase in level of glial-derived neurotrophic factor (GDNF) mRNA in both cell types. Similarly, the synthesis of GDNF protein was increased by both treatments. Interleukin-1beta (IL-1beta) and interferon-gamma (IFN-gamma) induced similar effects on GDNF production, whereas IL-2 and IL-6 had no significant effects. These results indicate that the expression of GDNF in astrocytes is regulated by inflammatory stimuli and therefore may provide neurotrophic support to injured neurons in inflammatory conditions in the CNS.
Appel
E
E
Department of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
Kolman
O
O
Kazimirsky
G
G
Blumberg
P M
PM
Brodie
C
C
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D051100:Glial Cell Line-Derived Neurotrophic Factor; D007249:Inflammation / Q000503:physiopathology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D009414:Nerve Growth Factors / Q000096:biosynthesis*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D015854:Up-Regulation / Q000187:drug effects
D016207:Cytokines; C495040:Gdnf protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D008070:Lipopolysaccharides; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger