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 immunologically important molecules, major histocompatibility complex class II (MHC-II) and nitric oxide (NO) following treatment with IFN-gamma and beta-amyloid (betaA) peptides, betaA(1-42) and betaA(25-35). IFN-gamma is a potent inducer of both MHC-II gene expression and NO production. The induction of MHC-II was inhibited by both betaA peptides in astrocytes but they had little or no effect in microglia. betaA peptides had no effect on NO release in astrocytes but on microglia betaA(1-42) synergistically induced NO release with IFN-gamma. Transient transfection of astrocytes with 5' deletional mutants of MHC-II IAalpha promoter linked to the chloramphenicol acetyl transferase reporter gene (IAalpha-CAT), demonstrated that betaA acts at the transcriptional level to downregulate IFN-gamma induced MHC-II gene expression in astrocytes. In previous studies, the induction of MHC-II on glial cells were suggested to be involved in the pathogenesis of neurodegenerative diseases and MHC-II(+) microglial cells were observed at much higher frequency than astrocytes. This study provides information on the regulation of the MHC-II gene expression in astrocytes and in microglial cells by betaA and this pathway may be critically involved in the immune/inflammatory regulation within the central nervous system.
Pazmany
T
T
Gedeon Richter Ltd., Budapest 1103, Gyomroi u.19-21, Hungary. tpazmany@richter.hu
Mechtler
L
L
Tomasi
T B
TB
Kosa
J P
JP
Turoczi
A
A
Urbanyi
Z
Z
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000502:physiology*; D005802:Genes, MHC Class II; D007371:Interferon-gamma / Q000494:pharmacology; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016229:Amyloid beta-Peptides; D009569:Nitric Oxide; D007371:Interferon-gamma