Differential regulation of major histocompatibility complex class II expression and nitric oxide release by beta-amyloid in rat astrocyte and microglia

Astrocytes and microglial cells were examined for expression of two immunol ogically important molecules, major histocompatibility complex class II (MH C-II) and nitric oxide (NO) following treatment with IFN-gamma and beta-amy loid (beta A) peptides, beta A(1-42) and beta A(25-35). IFN-gamma is a pote nt inducer of both MHC-II gene expression and NO production. The induction of MHC-II was inhibited by both beta A peptides in astrocytes but they had little or no effect in microglia. beta A peptides had no effect on NO relea se in astrocytes but on microglia PA(1-42) synergistically induced NO relea se with IFN-gamma. Transient transfection of astrocytes with 5' deletional mutants of MHC-II IA alpha promoter linked to the chloramphenicol acetyl tr ansferase reporter gene (IA alpha-CAT), demonstrated that beta A acts at th e transcriptional level to downregulate IFN-gamma induced MHC-II gene expre ssion in astrocytes. In previous studies, the induction of MHC-II on glial cells were suggested to be involved in the pathogenesis of neurodegenerativ e diseases and MHC-II+ microglial cells were observed at much higher freque ncy than astrocytes. This study provides information on the regulation of t he MHC-II gene expression in astrocytes and in microglial cells by beta A a nd this pathway may be critically involved in the immune/inflammatory regul ation within the central nervous system. (C) 1999 Elsevier Science B.V. All rights reserved.