IL-1p INDUCES GFAP EXPRESSION IN VITRO AND IN VIVO AND PROTECTS NEURONS FROM TRAUMATIC INJURY-ASSOCIATED APOPTOSIS IN RAT BRAIN STRIATUM VIA NFkB/CA2+-CALMODULIN/ERK MITOGEN-ACTIVATED PROTEIN KINASE SIGNALING PATHWAY

摘要

Reactive astrogliosis, a feature of neuro-inflam-mation is induced by a number of endogenous mediators including cytokines. Despite interleukin-1 beta (IL-ibeta) stands out as the major inducer of this process, the underlying mechanism and its role on neuronal viability remain elusive. We investigated in human astrocytoma cells and the rat brain striatum, the role of the nuclear factor-kB (NF-kB) intracellular Ca2+ concentration ([Ca2+]i) calmodulin (CaM) and extracellular regulated mitogen-activated protein kinases (ERK1/2) in IL-ibeta-induced expression of glial fibril-lary acidic protein (GFAP) and neuronal apoptosis associated to a brain trauma. Cell data showed that IL-ibeta (1 ng/ ml) increased NF-kB, pERK1/2 and GFAP expression. Nevertheless, further increase in IL-1 beta levels reversed progressively these responses. Preventing ERK1/2 activation with 1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthiol]-butadi-ene antagonized IL-ip-induced GFAP expression while inhibiting selectively nuclear translocation of NF-kB with caffeic-acid phenethyl-ester down-regulated both ERK1/2 and GFAP expression induced by IL-1 beta.