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Accession: PRJNA105707 ID: 105707

Homo sapiens (human)

Gene expression analysis of macrophages from ankylosing spondylitis patients reveals interferon-gamma dysregulation

See Genome Information for Homo sapiens
OBJECTIVE: To determine whether macrophages, a type of cell implicated in the pathogenesis of ankylosing spondylitis (AS), exhibit a characteristic gene expression pattern. METHODS: Macrophages were derived from the peripheral blood of 8 AS patients (median disease duration 13 years [range <1-43 years]) and 9 healthy control subjects over 7 days with the use of granulocyte-macrophage colony-stimulating factor. Cells were stimulated for 24 hours with interferon-gamma (IFNgamma; 100 units/ml), were left untreated for 24 hours, or were treated for 3 hours with lipopolysaccharide (LPS; 10 ng/ml). RNA was isolated and examined by microarray and real-time quantitative reverse transcription-polymerase chain reaction analysis. RESULTS: Microarray analysis revealed 198 probe sets detecting the differential expression of 141 unique genes in untreated macrophages from AS patients compared with healthy controls. Clustering and principal components analysis clearly distinguished AS patients and controls. Of the differentially expressed genes, 78 (55%) were IFN-regulated, and their relative expression indicated a reverse IFN signature in AS patient macrophages, where IFNgamma-up-regulated genes were underexpressed and down-regulated genes were overexpressed. Treatment of macrophages with exogenous IFNgamma normalized the expression of these genes between patients and controls. In addition, the messenger RNA encoded by the IFNgamma gene was approximately 2-fold lower in AS patient macrophages at baseline (P = 0.004) and was poorly responsive to LPS (P = 0.018), as compared with healthy controls. CONCLUSIONS: Our findings reveal consistent differences in gene expression in macrophages from AS patients, with evidence of a striking reverse IFN signature. Together with poor expression and responsiveness of the IFNgamma gene, these results suggest that there may be a relative defect in IFNgamma gene regulation, with autocrine consequences and implications for disease pathogenesis. Keywords: Disease state analysis with treatment effect Overall design: Macrophages were derived from the peripheral blood of 8 AS patients (median disease duration 13 years [range <1–43 years]) and 9 healthy control subjects over 7 days with the use of granulocyte– macrophage colony-stimulating factor. Cells were stimulated for 24 hours with interferon- (IFN; 100 units/ ml), were left untreated for 24 hours, or were treated for 3 hours with lipopolysaccharide (LPS; 10 ng/ml). RNA was isolated and examined by microarray and real-time quantitative reverse transcription–polymerase chain reaction analysis.
AccessionPRJNA105707; GEO: GSE11886
Data TypeTranscriptome or Gene expression
ScopeMultiisolate
OrganismHomo sapiens[Taxonomy ID: 9606]
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo; Homo sapiens
PublicationsSmith JA et al., "Gene expression analysis of macrophages derived from ankylosing spondylitis patients reveals interferon-gamma dysregulation.", Arthritis Rheum, 2008 Jun;58(6):1640-9
SubmissionRegistration date: 27-Jun-2008
Dr. David Glass, Rheumatology, Cincinnati Childrens Hospital Medical Center
RelevanceMedical
Project Data:
Resource NameNumber
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PubMed1
PMC1
Other datasets
GEO DataSets1
GEO Data Details
ParameterValue
Data volume, Spots1804275
Data volume, Processed Mbytes39
Data volume, Supplementary Mbytes198

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