title: Activation of the JAK/STAT pathway in Behcet's disease.
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.
authors.affiliation: Division of Immunology, Department of Internal Medicine, Marmara University, School of Medicine Hospital, Istanbul, Turkey.
authors.forename: A
authors.identifier: 0000000347359902
authors.initials: A
authors.lastname: Tulunay
authors.affiliation: 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.
authors.forename: M G
authors.initials: MG
authors.lastname: Dozmorov
authors.affiliation: Division of Immunology, Department of Internal Medicine, Marmara University, School of Medicine Hospital, Istanbul, Turkey.
authors.forename: F
authors.initials: F
authors.lastname: Ture-Ozdemir
authors.affiliation: Department of Physiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: V
authors.initials: V
authors.lastname: Yilmaz
authors.affiliation: Division of Immunology, Department of Internal Medicine, Marmara University, School of Medicine Hospital, Istanbul, Turkey.
authors.forename: E
authors.initials: E
authors.lastname: Eksioglu-Demiralp
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Marmara University, School of Medicine Hospital, Istanbul, Turkey.
authors.forename: F
authors.initials: F
authors.lastname: Alibaz-Oner
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Marmara University, School of Medicine Hospital, Istanbul, Turkey.
authors.forename: G
authors.initials: G
authors.lastname: Ozen
authors.affiliation: 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.
authors.forename: J D
authors.initials: JD
authors.lastname: Wren
authors.affiliation: Department of Physiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: G
authors.initials: G
authors.lastname: Saruhan-Direskeneli
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
authors.forename: A H
authors.initials: AH
authors.lastname: Sawalha
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Marmara University, School of Medicine Hospital, Istanbul, Turkey.
authors.forename: H
authors.initials: H
authors.lastname: Direskeneli
mesh_terms: D000328:Adult; D001528:Behcet Syndrome / Q000201:enzymology / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study; D006801:Humans; D007378:Interleukins / Q000378:metabolism; D053613:Janus Kinase 1 / Q000276:immunology / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D008297:Male; D050796:STAT3 Transcription Factor / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology
chemical_list: D007378:Interleukins; D018950:Lipopolysaccharide Receptors; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C507904:JAK1 protein, human; D053613:Janus Kinase 1