Transforming growth factor β1 and laminin-111 cooperate in the induction of interleukin-16 expression in synovial fibroblasts from patients with rheumatoid arthritis
| Autor: | Warstat, K, Hoberg, M, Rudert, M, Tsui, S, Pap, T, Angres, B, Essl, M, Smith, T J, Cruikshank, W W, Klein, G, Gay, S, Aicher, W K |
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| Rok vydání: | 2009 |
| Předmět: |
Immunology
Integrin Arthritis General Biochemistry Genetics and Molecular Biology Laminin 111 Proinflammatory cytokine Arthritis Rheumatoid Transforming Growth Factor beta1 03 medical and health sciences 0302 clinical medicine Rheumatology Laminin Osteoarthritis Cell Adhesion medicine Humans Immunology and Allergy RNA Messenger Cells Cultured 030304 developmental biology Interleukin-16 0303 health sciences biology business.industry Synovial Membrane Fibroblasts medicine.disease medicine.anatomical_structure biology.protein Cancer research Synovial membrane Interleukin 16 business Signal Transduction 030215 immunology Transforming growth factor |
| Zdroj: | Annals of the Rheumatic Diseases |
| ISSN: | 1468-2060 0003-4967 |
| Popis: | Objectives:In synovial tissues of patients with rheumatoid arthritis (RA), strong expression of laminins and integrins co-localises with increased expression of inflammatory cytokines. Synovial fibroblasts (SF) contribute to the pathogenesis of RA through increased expression of cytokines and chemoattractant factors, one of which is interleukin-16 (IL16). A study was undertaken to investigate the regulatory pathways of IL16 in SF from patients with RA (RA-SF) and osteoarthritis (OA-SF).Methods:SF were seeded in laminin-coated flasks and activated by the addition of cytokines. The expression of IL16 was investigated by quantitative RT-PCR, immunoblotting and ELISA; its biological activity was determined by a cell migration assay. Cell–matrix interactions were investigated by cell binding and attachment assays. Relevant intracellular signalling pathways were studied by immunoblotting and with pharmacological blocking reagents.Results:Stimulation of SF with transforming growth factor β1 (TGF-β1) and growth on laminin-111 (LM-111) significantly increased the expression of IL16. Binding to LM-111 induced significantly more IL16 mRNA in RA-SF than in OA-SF (p1-activated and in LM-111+TGF-β1-activated RA-SF (38 to 62 pg/ml), but not in supernatants of OA-SF. This IL16 regulation involved p38MAPK, ERK1/2 and SMAD2 signalling, but not NFκB.Conclusions:Binding of RA-SF to LM-111 in the presence of TGF-β1 triggers a significant IL16 response and thus may contribute to the infiltration of CD4+ lymphocytes into synovial tissues. This mode of IL16 induction represents a novel pathway leading to IL16 production in RA-SF but not in OA-SF, which operates independently of NFκB signalling. |
| Databáze: | OpenAIRE |
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