RGD Reference Report - Analysis of genes differentially expressed in astrocytes stimulated with lipopolysaccharide using cDNA arrays. - Rat Genome Database

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Analysis of genes differentially expressed in astrocytes stimulated with lipopolysaccharide using cDNA arrays.

Authors: Pang, Y  Cai, Z  Rhodes, PG 
Citation: Pang Y, etal., Brain Res. 2001 Sep 28;914(1-2):15-22.
RGD ID: 1599044
Pubmed: PMID:11578593   (View Abstract at PubMed)

We used cDNA arrays to investigate differentially expressed genes in astrocytes challenged with lipopolysaccharide (LPS). Astrocyte cultures were prepared from 1-day-old rat brains. Purified astrocytes were treated with LPS (1 microg/ml) for 2, 8 and 48 h. Differentially expressed genes in these astrocytes were examined with Atlas rat cDNA arrays. At all the three time points studied, three genes were found consistently up-regulated: I-kappaB alpha chain, NF-kappaB, and interferon induced protein. In addition to these three, six other genes were also up-regulated at 2 and 8 h. They were genes encoding vascular cell adhesion protein 1 (VCAM-1), interferon regulatory factor 1 (IRF-1), mitochondrial hydroxymethylglutaryl-CoA synthase (HMG-CoA synthase), aldehyde dehydrogenase 2, macrophage inflammatory protein 1 (MIP-1) and neurotensin receptor 2. At these two time points, three genes were down-regulated: copper-zinc-containing superoxide dismutase 1 (SOD-1), insulin-like growth factor binding protein 1 (IGFBP-1), and insulin-like growth factor binding protein 3 (IGFBP-3). Expression of several differentially expressed genes in cDNA array (I-kappaB, VCAM-1 and MIP-3) were further confirmed by reverse transcription polymerase chain reaction study. The prominently modulated genes could be classified into three categories: nuclear transcription factors, pro-inflammatory cytokines/chemokines and metabolic enzymes. Application of pyrrolidine dithiocarbamate, an inhibitor of nuclear factor-kB (NF-kappaB), prior to LPS stimulation not only prevented up-regulation of NF-kappaB gene expression, but also completely blocked up-regulation of pro-inflammatory cytokine genes (TNF-alpha and interleukin-1beta) and two chemokine genes: CXC chemokine LIX and CC chemokine MIP-3 alpha. These results indicate that both up-regulation of inflammatory cytokine expression and down-regulation of growth factor expression are probably involved in the response of astrocytes upon exposure to LPS.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cellular response to lipopolysaccharide  IEP 1599044 RGD 
response to lipopolysaccharide  IEP 1599044 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Aldh2  (aldehyde dehydrogenase 2 family member)
Hmgcs2  (3-hydroxy-3-methylglutaryl-CoA synthase 2)


Additional Information