Anti-beta2GPI-antibody-induced endothelial cell gene expression profiling reveals induction of novel pro-inflammatory genes potentially involved in primary antiphospholipid syndrome.

2.50
Hdl Handle:
http://hdl.handle.net/2436/29438
Title:
Anti-beta2GPI-antibody-induced endothelial cell gene expression profiling reveals induction of novel pro-inflammatory genes potentially involved in primary antiphospholipid syndrome.
Authors:
Hamid, Colleen G.; Norgate, K.; D'Cruz, D.P.; Khamashta, M.A.; Arno, M.; Pearson, J.D.; Frampton, Geoffrey; Murphy, John J.
Abstract:
OBJECTIVE: To determine the effects of primary antiphospholipid syndrome (PAPS)-derived anti-beta(2)GPI antibodies on gene expression in human umbilical vein endothelial cells (HUVEC) by gene profiling using microarrays. METHODS: Anti-beta(2)GPI antibodies purified from sera of patients with PAPS or control IgG isolated from normal subjects were incubated with HUVEC for 4 h before isolation of RNA and processing for hybridisation to Affymetrix Human Genome U133A-2.0 arrays. Data were analysed using a combination of the MAS 5.0 (Affymetrix) and GeneSpring (Agilent) software programmes. For selected genes microarray data were confirmed by real-time PCR analysis or at the protein level by ELISA. RESULTS: A total of 101 genes were found to be upregulated and 14 genes were downregulated twofold or more in response to anti-beta(2)GPI antibodies. A number of novel genes not previously associated with APS were induced, including chemokines CCL20, CXCL3, CX3CL1, CXCL5, CXCL2 and CXCL1, the receptors Tenascin C, OLR1, IL-18 receptor 1, and growth factors CSF2, CSF3 IL-6, IL1beta and FGF18. The majority of downregulated genes were transcription factors/signalling molecules including ID2. Quantitative real-time RT-PCR analysis confirmed the microarray results for selected genes (CSF3, CX3CL1, FGF18, ID2, SOD2, Tenascin C). CONCLUSIONS: This study reveals a complex gene expression response in HUVEC to anti-beta(2)GPI antibodies with multiple chemokines, pro-inflammatory cytokines, pro-thrombotic and pro-adhesive genes regulated by these antibodies in vitro. Some of these newly identified anti-beta(2)GPI antibody-regulated genes could contribute to the vasculopathy associated with this disease.
Citation:
Annals of the Rheumatic Diseases, 66 (8): 1000-7
Publisher:
BMJ Publishing & European League Against Rheumatism
Journal:
Annals of the Rheumatic Diseases
Issue Date:
2007
URI:
http://hdl.handle.net/2436/29438
DOI:
10.1136/ard.2006.063909
PubMed ID:
17223652
Additional Links:
http://ard.bmj.com/cgi/content/full/66/8/1000
Type:
Article
Language:
en
ISSN:
0003-4967
Appears in Collections:
Food Biology, Medical Microbiology and Disinfection Research Group

Full metadata record

DC FieldValue Language
dc.contributor.authorHamid, Colleen G.-
dc.contributor.authorNorgate, K.-
dc.contributor.authorD'Cruz, D.P.-
dc.contributor.authorKhamashta, M.A.-
dc.contributor.authorArno, M.-
dc.contributor.authorPearson, J.D.-
dc.contributor.authorFrampton, Geoffrey-
dc.contributor.authorMurphy, John J.-
dc.date.accessioned2008-06-04T09:34:40Z-
dc.date.available2008-06-04T09:34:40Z-
dc.date.issued2007-
dc.identifier.citationAnnals of the Rheumatic Diseases, 66 (8): 1000-7en
dc.identifier.issn0003-4967-
dc.identifier.pmid17223652-
dc.identifier.doi10.1136/ard.2006.063909-
dc.identifier.urihttp://hdl.handle.net/2436/29438-
dc.description.abstractOBJECTIVE: To determine the effects of primary antiphospholipid syndrome (PAPS)-derived anti-beta(2)GPI antibodies on gene expression in human umbilical vein endothelial cells (HUVEC) by gene profiling using microarrays. METHODS: Anti-beta(2)GPI antibodies purified from sera of patients with PAPS or control IgG isolated from normal subjects were incubated with HUVEC for 4 h before isolation of RNA and processing for hybridisation to Affymetrix Human Genome U133A-2.0 arrays. Data were analysed using a combination of the MAS 5.0 (Affymetrix) and GeneSpring (Agilent) software programmes. For selected genes microarray data were confirmed by real-time PCR analysis or at the protein level by ELISA. RESULTS: A total of 101 genes were found to be upregulated and 14 genes were downregulated twofold or more in response to anti-beta(2)GPI antibodies. A number of novel genes not previously associated with APS were induced, including chemokines CCL20, CXCL3, CX3CL1, CXCL5, CXCL2 and CXCL1, the receptors Tenascin C, OLR1, IL-18 receptor 1, and growth factors CSF2, CSF3 IL-6, IL1beta and FGF18. The majority of downregulated genes were transcription factors/signalling molecules including ID2. Quantitative real-time RT-PCR analysis confirmed the microarray results for selected genes (CSF3, CX3CL1, FGF18, ID2, SOD2, Tenascin C). CONCLUSIONS: This study reveals a complex gene expression response in HUVEC to anti-beta(2)GPI antibodies with multiple chemokines, pro-inflammatory cytokines, pro-thrombotic and pro-adhesive genes regulated by these antibodies in vitro. Some of these newly identified anti-beta(2)GPI antibody-regulated genes could contribute to the vasculopathy associated with this disease.en
dc.language.isoenen
dc.publisherBMJ Publishing & European League Against Rheumatismen
dc.relation.urlhttp://ard.bmj.com/cgi/content/full/66/8/1000en
dc.subject.meshAdulten
dc.subject.meshAntigen-Antibody Reactionsen
dc.subject.meshAntiphospholipid Syndromeen
dc.subject.meshAutoantibodiesen
dc.subject.meshCase-Control Studiesen
dc.subject.meshDown-Regulationen
dc.subject.meshE-Selectinen
dc.subject.meshEndothelial Cellsen
dc.subject.meshFemaleen
dc.subject.meshGene Expression Profilingen
dc.subject.meshHumansen
dc.subject.meshImmunoglobulin Gen
dc.subject.meshInterleukin-8en
dc.subject.meshMiddle Ageden
dc.subject.meshOligonucleotide Array Sequence Analysisen
dc.subject.meshbeta 2-Glycoprotein Ien
dc.titleAnti-beta2GPI-antibody-induced endothelial cell gene expression profiling reveals induction of novel pro-inflammatory genes potentially involved in primary antiphospholipid syndrome.en
dc.typeArticleen
dc.identifier.journalAnnals of the Rheumatic Diseasesen
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