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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-18623

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 (2009). TGF-{beta}1 and laminin-111 cooperate in the induction of IL-16 expression in synovial fibroblasts from rheumatoid arthritis patients. Annals of the Rheumatic Diseases, 69(1):270-275.

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OBJECTIVES: In synovial tissues of rheumatoid arthritis (RA) patients strong expression of laminins and integrins co-localizes with elevated expression of inflammatory cytokines. Synovial fibroblasts (SF) contribute to the pathogenesis of RA through elevated expression of cytokines and chemoattractant factors, one of which is IL-16. We therefore investigated regulatory pathways of IL-16 in SF from RA and osteoarthritis (OA) patients. METHODS: SF were seeded in laminin-coated flasks and activated by the addition of cytokines. Expression of IL-16 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 signaling pathways were studied by immunoblotting and with pharmacological blocking reagents. RESULTS: The stimulation of SF with TGF-beta1 and growth on laminin-111 (LM-111) significantly increased the expression of IL-16. In RA-SF, binding to LM-111 induced significantly more IL-16 mRNA than in OA-SF (p<0.05). The IL-16 cytokine was detected in supernatants of TGF-beta1-activated and in LM-111 plus TGF-beta1-activated RA-SF (38 to 62 pg/ml), but not in supernatants of OA-SF. This IL-16 regulation involved p38MAPK, ERK1/2 and SMAD2 signaling, but not NFkappaB. CONCLUSIONS: Binding of RA-SF to LM-111 in the presence of TGF-beta1 triggers a significant IL-16 response and thus may contribute to the infiltration of CD4+ lymphocytes into synovial tissues. This mode of IL-16 induction represents a novel pathway leading to IL-16 production in RA-SF but not in OA-SF, and it operates independently of NFkappaB signaling.


8 citations in Web of Science®
9 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Rheumatology Clinic and Institute of Physical Medicine
Dewey Decimal Classification:610 Medicine & health
Date:10 March 2009
Deposited On:25 May 2009 04:35
Last Modified:05 Apr 2016 13:13
Publisher:BMJ Publishing Group
Publisher DOI:10.1136/ard.2008.091116
PubMed ID:19279017

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