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 th e expression of glial fibrillary acidic protein (GFAP), the most specific m arker 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 activat ion of the mitogen activated protein kinase (MAPK) Erk2 (extracellular sign al-regulated protein kinase). We also demonstrate chat TNF-alpha-induced ov er-expression of GFAP was significantly attenuated by the MAPK inhibitor PD 98059. We conclude that TNF-alpha may upregulate GFAP through the MAPK sign aling pathway. Because increased GFAP is a hallmark of reactive gliosis, un derstanding the mechanisms that regulate GFAP expression may facilitate dev elopment of strategies to minimize the gliosis associated with many brain d iseases. NeuroReport 11:409-412 (C) 2000 Lippincott Williams & Wilkins.