Activation of the STAT1 pathway in rheumatoid arthritis. Issue 3 (12th February 2004)

• Record Type: Journal Article
• Authors: Kasperkovitz, P V; Verbeet, N L; Smeets, T J; van Rietschoten, J G I; Kraan, M C; van der Pouw Kraan, T C T M; Tak, P P; Verweij, C L
• Is Part Of: Annals of the rheumatic diseases. Volume 63:Issue 3(2004)
• Page Start: 233
• Page End: 239
• Publication Date: 2004-02-12
• Subjects: STAT1 -- phosphorylation -- rheumatoid arthritis -- synovium -- synoviocytes; ACR, American College of Rheumatology -- AP, alkaline phosphatase -- BSA, bovine serum albumin -- DMARD, disease modifying antirheumatic drug -- FCS, fetal calf serum -- FITC, fluorescein isothiocyanate -- HPF, high power field -- HRP, horseradish peroxidase -- IFM, immunofluorescence microscopy -- IFN, interferon -- IHC, immunohistochemistry -- IOD, integrated optical density -- OA, osteoarthritis -- RA, rheumatoid arthritis -- ReA, reactive arthritis -- ST, synovial tissue -- STAT, signal transducer and activator of transcription; Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/ard.2003.013276
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: Expression of signal transducer and activator of transcription 1 (STAT1), the mediator of interferon (IFN) signalling, is raised in synovial tissue (ST) from patients with rheumatoid arthritis (RA). Objectives: To determine the extent to which this pathway is activated by phosphorylation in RA synovium. Additionally, to investigate the cellular basis of STAT1 activation in RA ST. Methods: ST specimens from 12 patients with RA and 14 disease controls (patients with osteoarthritis and reactive arthritis) were analysed by immunohistochemistry, using antibodies to STAT1, tyrosine phosphorylated STAT1, and serine phosphorylated STAT1. Lysates of cultured fibroblast-like synoviocytes stimulated with IFNβ were analysed by western blotting. Phenotypic characterisation of cells expressing STAT1 in RA ST was performed by double immunolabelling for STAT1 and CD3, CD22, CD55, or CD68. Results: Raised levels of total STAT1 protein and both its activated tyrosine and serine phosphorylated forms were seen in RA synovium as compared with controls. STAT1 was predominantly abundant in T and B lymphocytes in focal inflammatory infiltrates and in fibroblast-like synoviocytes in the intimal lining layer. Raised levels of STAT1 are sustained in cultured RA compared with OA fibroblast-like synoviocytes, and STAT1 serine and tyrosine phosphorylation is rapidly induced upon stimulation with IFNβ. Conclusion: These results demonstrate activation of the STAT1 pathway in RA synovium by raised STAT1 protein expression and concomitantly increased tyrosine (701) and serine (727) phosphorylation. High expression of STAT1 is intrinsic to RA fibroblast-like synoviocytes in the intimal lining layer, whereas activation of the pathway by phosphorylation is an active process.