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Genes Immun. 2015 Mar;16(2):170-5. doi: 10.1038/gene.2014.64. Epub 2014 Nov 20.

Activation of the JAK/STAT pathway in Behcet's disease.

Author information

1
Division of Immunology, Department of Internal Medicine, Marmara University, School of Medicine Hospital, Istanbul, Turkey.
2
1] Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation and Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA [2] Department of Biostatistics, Bioinformatic Section, Translational Research Informatics Core (TRI Core), Virginia Commonwealth University, Richmond, VA, USA.
3
Department of Physiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
4
Division of Rheumatology, Department of Internal Medicine, Marmara University, School of Medicine Hospital, Istanbul, Turkey.
5
Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation and Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
6
Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.

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 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-γ), IL-6, IL-17 and IL-23.

PMID:
25410656
PMCID:
PMC4443896
DOI:
10.1038/gene.2014.64
[Indexed for MEDLINE]
Free PMC Article

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