Activation of the JAK/STAT pathway in Behcet’s Disease

Aysin Tulunay; Mikhail G. Dozmorov; Filiz Ture-Ozdemir; Vuslat Yilmaz; Emel Eksioglu-Demiralp; Fatma Alibaz-Oner; Gülsen Ozen; Jonathan D. Wren; Guher Saruhan-Direskeneli; Amr H. Sawalha; Haner Direskeneli

doi:10.1038/gene.2014.64

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Activation of the JAK/STAT pathway in Behcet’s Disease

Journal article

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Activation of the JAK/STAT pathway in Behcet’s Disease

Aysin Tulunay, Mikhail G. Dozmorov, Filiz Ture-Ozdemir, Vuslat Yilmaz, Emel Eksioglu-Demiralp, Fatma Alibaz-Oner, Gülsen Ozen, Jonathan D. Wren, Guher Saruhan-Direskeneli, Amr H. Sawalha, …

Genes and immunity, Vol.16(2), pp.170-175

03/01/2015

DOI: 10.1038/gene.2014.64

PMCID: PMC4443896

PMID: 25410656

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Abstract

Th1/Th17-type T-cell responses are upregulated in Behcet’s disease (BD). However, signaling pathways associated with this aberrant immune response are not clarified. Whole-genome microarray profiling was performed with human U133 (Plus 2.0) chips using mRNA of isolated CD14 + monocytes and CD4 + T-cells from PBMC in patients with BD (n=9) and healthy controls (HC) (n=9). Flow cytometric analysis of unstimulated (US) and stimulated (PHA) STAT3 and pSTAT3 expressions of PBMCs were also analysed (BD and HC, both n=26). JAK1 was observed to be upregulated in both CD14 + monocytes (1.95 fold) and CD4 + T-lymphocytes (1.40 fold) of BD patients. Using canonical pathway enrichment analysis, JAK/STAT signaling was identified as activated in both CD14 + monocytes (p= 9.55E-03) and in CD4 + lymphocytes (p= 8.13E-04) in BD. Interferon signaling was also prominent among upregulated genes in CD14 + monocytes (p= 5.62E-05). Glucocorticoid receptor signaling and IL-6 signaling were among the most enriched pathways in differentially expressed genes in CD14+ monocytes (p= 2.45E-09, and 1.00E-06, respectively). Basal unstimulated total STAT3 expression was significantly higher in BD (1.2 vs 3.45, p<0.05). The JAK1/STAT3 signaling pathway is activated in BD, possibly through the activation of Th1/Th17-type cytokines such as IL-2, IFNγ, IL-6, IL-17 and IL-23.

Details

Title: Subtitle: Activation of the JAK/STAT pathway in Behcet’s Disease
Creators: Aysin Tulunay
Mikhail G. Dozmorov - University of Oklahoma Health Sciences Center
Filiz Ture-Ozdemir
Vuslat Yilmaz
Emel Eksioglu-Demiralp
Fatma Alibaz-Oner
Gülsen Ozen
Jonathan D. Wren - University of Oklahoma Health Sciences Center
Guher Saruhan-Direskeneli
Amr H. Sawalha - University of Michigan–Ann Arbor
Haner Direskeneli - Marmara University
Resource Type: Journal article
Publication Details: Genes and immunity, Vol.16(2), pp.170-175
DOI: 10.1038/gene.2014.64
PMID: 25410656
PMCID: PMC4443896
ISSN: 1466-4879
eISSN: 1476-5470
Number of pages: 6
Language: English
Date published: 03/01/2015
Academic Unit: Internal Medicine
Record Identifier: 9984702825502771

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