title: Cytokine-induced STAT1 activation is increased in patients with primary Sjögren's syndrome.
abstract: Limited data are available regarding the intracellular responses to different cytokines in primary Sjögren's syndrome (pSS). We studied the signal transducer and activator of transcription (STAT) activation profile in response to cytokine stimulations in peripheral blood mononuclear cells (PBMCs) from pSS patients by multicolor flow cytometry. The expression of the suppressors of cytokine signaling (SOCS), and interferon (IFN)-γ target genes in PBMCs was studied using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). The induction of STAT1 phosphorylation in response to stimulation with IFN-α, IFN-γ or interleukin (IL)-6 was significantly increased in B cells and monocytes from pSS patients. Accordingly, the STAT1-mediated gene responses were significantly enhanced in PBMCs from pSS patients. Finally, the expression of SOCS1 and SOCS3 mRNA was increased in pSS patients. The results indicate increased sensitivity of immune cells from pSS patients to STAT1-activating signals, and may partly explain the IFN signature observed in pSS.
authors.affiliation: Department of Internal Medicine, Centre for Rheumatic Diseases, Tampere University Hospital, Tampere, Finland; School of Medicine, University of Tampere, Tampere, Finland. Electronic address: marja.pertovaara@uta.fi.
authors.forename: Marja
authors.initials: M
authors.lastname: Pertovaara
authors.affiliation: School of Medicine, University of Tampere, Tampere, Finland; Department of Internal Medicine, Tampere University Hospital, Tampere, Finland.
authors.forename: Olli
authors.initials: O
authors.lastname: Silvennoinen
authors.affiliation: Department of Internal Medicine, Centre for Rheumatic Diseases, Tampere University Hospital, Tampere, Finland; School of Medicine, University of Tampere, Tampere, Finland.
authors.forename: Pia
authors.initials: P
authors.lastname: Isomäki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D050794:STAT1 Transcription Factor / Q000235:genetics* / Q000378:metabolism*; D012859:Sjogren's Syndrome / Q000503:physiopathology*; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D007371:Interferon-gamma
keywords: Interferon-α; Interferon-γ; Interleukin-6; Phosphorylation; STAT; Sjögren's syndrome