Microarray analysis of human primary astrocytes activated by beta amyloid peptide and alpha1-antichymotrypsin

Abstract

To investigate gene expression of astrocytes under the actions of amyloid peptide Abeta(1-42) and alpha1-antichymotrypsin (ACT) and to explore the characteristics of inflammatory reactions occurring in brain of Alzheimer's patients. Human primary astrocytes were cultured to the second passage and then treated with lipopolysaccharide (LPS), Abeta(1-42) (50 micromol/L) and Abeta(1-42)/ACT (50:5 micromol/L) respectively. At 24 h, cells were harvested for total RNA extraction. Gene expression profile was screened by microarray technique. And the function enrichment of differentially expressed genes and the signal transduction pathways involved were analyzed. In comparison with LPS, both Abeta(1-42) and Abeta(1-42)/ACT had demonstrated marked effects on altering the astrocyte gene expression. And the gene up-regulation was predominant. But the gene expression spectrum varied between different groups. Gene ontology analysis showed that Abeta(1-42) up-regulated genes modulated inflammation, oxidative stress and immune response. But Abeta(1-42)/ACT had significant effects on genes related with mitochondrial impairment, apoptosis, oxidative stress, epithelial differentiation and vasculogenesis. The analysis of up-regulated genes, such as interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFalpha), showed that transcriptional factors and downstream genes of signal transduction pathways potentiated further the inflammatory response and cell apoptosis and increased the production of abnormal Abeta. Abeta(1-42) induces the inflammation of astrocytes. And the Abeta(1-42)/ACT complex has diverse effects on the gene expression of astrocytes. Thus both proteins play important roles in the activation of astrocytes. In addition, IL-6, TNFalpha and their signal pathways are important in the pathogenic process of Alzheimer's disease.