Activation of the JAK/STAT pathway in Behcet's disease (vol 16, pg 176, 2015)

被引:12
作者
Tulunay, A.
Dozmorov, M. G.
Ture-Ozdemir, F.
Yilmaz, V.
Eksioglu-Demiralp, E.
Alibaz-Oner, F.
Ozen, G.
Wren, J. D.
Saruhan-Direskeneli, G.
Sawalha, A. H.
Direskeneli, H.
机构
[1] Division of Immunology, Department of Internal Medicine, Marmara University, School of Medicine Hospital, Istanbul
[2] Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Department of Biochemistry and Molecular Biology, University of Oklahoma, Health Sciences Center, Oklahoma City, OK
[3] Department of Biostatistics, Bioinformatic Section, Translational Research Informatics Core (TRI Core), Virginia Commonwealth University, Richmond, VA
[4] Department of Physiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul
[5] Division of Rheumatology, Department of Internal Medicine, Marmara University, School of Medicine Hospital, Fevzi Çakmak Mahallesi, Mimar Sinan Caddesi, No. 41, Üst Kaynarca, Pendik, Istanbul
[6] Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI
关键词
D O I
10.1038/gene.2014.80
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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 messenger RNA of isolated CD14(+) monocytes and CD4(+) T cells from peripheral blood mononucleated cell (PBMC) in patients with BD (n = 9) and healthy controls (HCs) (n = 9). Flow cytometric analysis of unstimulated (US) and stimulated (phytohaemagglutinin) signal transducer and activator of transcription (STAT3) and pSTAT3 expressions of PBMCs were also analyzed (BD and HC, both n = 26). Janus family of kinase (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 interleukin (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 US 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, interferon (IFN-gamma), IL-6, IL-17 and IL-23.
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页码:176 / 176
页数:1
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2015, FENES