TNF-alpha induced over-expression of GFAP is associated with MAPKs.
Increased levels of tumor necrosis factor-alpha (TNF-alpha), a pluripotent cytokine that is reportedly mitogenic to astrocytes, are associated with the expression of glial fibrillary acidic protein (GFAP), the most specific marker for astrocytes, in many neuropathological conditions, including brain injury, CNS infection, Creutzfeldt-Jakob disease and Alzheimer's disease. Here, we show that treatment of cultured astrocytes with TNF-alpha resulted in dramatic over-expression of GFAP, associated with a substantial activation of the mitogen activated protein kinase (MAPK) Erk2 (extracellular signal-regulated protein kinase). We also demonstrate that TNF-alpha-induced over-expression of GFAP was significantly attenuated by the MAPK inhibitor PD98059. We conclude that TNF-alpha may upregulate GFAP through the MAPK signaling pathway. Because increased GFAP is a hallmark of reactive gliosis, understanding the mechanisms that regulate GFAP expression may facilitate development of strategies to minimize the gliosis associated with many brain diseases.
Zhang
L
L
Behavioral Endocrinology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.
Zhao
W
W
Li
B
B
Alkon
D L
DL
Barker
J L
JL
Chang
Y H
YH
Wu
M
M
Rubinow
D R
DR
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D002478:Cells, Cultured; D003720:Densitometry; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis*; D007150:Immunohistochemistry; D020935:MAP Kinase Signaling System / Q000187:drug effects; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D005419:Flavonoids; D005904:Glial Fibrillary Acidic Protein; D014409:Tumor Necrosis Factor-alpha; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one