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Series GSE38351 Query DataSets for GSE38351
Status Public on Jun 14, 2012
Title The multifaceted balance of TNF-a and type I / II interferon responses in SLE and RA: how monocytes manage the impact of cytokines
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Many cytokines are involved in the pathogenesis of autoimmune diseases and are recognized as relevant therapeutic targets to attenuate inflammation, such as TNFα in RA and IFNα/γ in SLE. To relate the transcriptional imprinting of cytokines in a cell type-specific and disease-specific manner, we generated gene-expression profiles from peripheral monocytes of SLE and RA patients and compared them to in vitro-generated signatures induced by TNFα, IFNα2a and IFNγ. Monocytes from SLE and RA patients revealed disease-specific gene-expression profiles. In vitro-generated signatures induced by IFNα2a and IFNγ showed similar profiles that only partially overlapped with those induced by TNFα. Comparisons between disease-specific and in vitro-generated signatures identified cytokine-regulated genes in SLE and RA with qualitative and quantitative differences. The IFN-responses in SLE and RA were found to be regulated in a STAT1-dependent and STAT1-independent manner, respectively. Similarly, genes recognized as TNFα-regulated were clearly distinguishable between RA and SLE patients. While the activity of SLE monocytes was mainly driven by IFN, the activity from RA monocytes showed a dominance of TNFα that was characterized by STAT1 down-regulation. The responses to specific cytokines were revealed to be disease-dependent and reflected the interplay of cytokines within various inflammatory milieus. This study has demonstrated that monocytes from RA and SLE patients exhibit disease-specific gene-expression profiles, which can be molecularly dissected when compared to in vitro-generated cytokine signatures. The results suggest that an assessment of cytokine-response status in monocytes may be helpful for improvement of diagnosis and selection of the best cytokine target for therapeutic intervention.
 
Overall design Expression profiles of human peripheral blood monocytes activated in vivo and stimulated in vitro. Monocytes from patients with SLE and RA and from healthy donors were used for generating disease-specific gene-expression profiles, where these profiles represent in vivo activation of monocytes. In addition, monocytes from healthy donors were stimulated in vitro by cytokines: TNFα, IFNα2a and IFNγ. Cytokine-specific gene-expression profiles were generated by comparing stimulated monocytes with unstimulated ones. TNFα-, IFNα2a- and IFNγ as cytokine-specific gene-expression profiles were compared with RA and SLE, as disease-specific gene-expression profiles.
Web link https://www.researchgate.net/publication/269873010
 
Contributor(s) Smiljanovic B, Grün JR, Biesen R, Schulte-Wrede U, Baumgrass R, Stuhlmüller B, Maslinski W, Hiepe F, Burmester G, Radbruch A, Häupl T, Grützkau A
Citation(s) 22610275, 19265543
Submission date May 30, 2012
Last update date Mar 25, 2019
Contact name Pawel Durek
E-mail(s) pawel.durek@drfz.de
Organization name Deutsches Rheuma-Forschungszentrum
Street address Charitéplatz 1
City Berlin
ZIP/Postal code 10117
Country Germany
 
Platforms (2)
GPL96 [HG-U133A] Affymetrix Human Genome U133A Array
GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
Samples (74)
GSM940450 Monocytes from SLE patient number 1 (SL_1)
GSM940451 Monocytes from SLE patient number 2 (SL_2)
GSM940452 Monocytes from SLE patient number 3 (SL_3)
Relations
BioProject PRJNA168483

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE38351_RAW.tar 292.8 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table
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