Chemokine Secretion of Rheumatoid Arthritis Synovial Fibroblasts Stimulated by Toll-Like Receptor 2 Ligands

Pierer, Matthias; Rethage, Janine; Seibl, Reinhart; Lauener, Roger; Brentano, Fabia; Wagner, Ulf; Häntzschel, H; Michel, Beat A.; Gay, Renate E.; Gay, Steffen; Kyburz, Diego

doi:10.4049/jimmunol.172.4.2704-b

Cited by 25 publications

(35 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…To define low and high inflammatory subtypes, we analysed gene identities in the subclusters (A to E) displaying clearly differential gene expression between subgroups (figure 5B). Consistent with prior studies, group III could be classified as a high inflammatory subtype based on significantly increased expression of genes involved in chemotaxis, angiogenesis and transforming growth factor β/activin A pathways 10 25 26…”

Section: Resultssupporting

confidence: 78%

A novel Saa3-promoter reporter distinguishes inflammatory subtypes in experimental arthritis and human synovial fibroblasts

Geurts

Vermeij²,

Pohlers³

et al. 2011

Annals of the Rheumatic Diseases

View full text Add to dashboard Cite

show abstract

Section: Resultssupporting

confidence: 78%

A novel Saa3-promoter reporter distinguishes inflammatory subtypes in experimental arthritis and human synovial fibroblasts

Geurts

Vermeij²,

Pohlers³

et al. 2011

Annals of the Rheumatic Diseases

View full text Add to dashboard Cite

show abstract

“…In contrast to our results, peptidoglycan not only induced the expression of MMP-3 but also seemed able to up-regulate the expression of other MMPs, such as MMP-1, MMP-9, and MMP-13 [16]. Furthermore, this bacterial component up-regulated the expression of several chemokine genes, including RANTES (regulated upon activation, normal T-cell expressed and secreted) and MCP-1 (monocyte chemoattractant protein-1) [30], but these genes were not represented on the arrays used in this study. These data indicate that various PRRs present on FLSs may contribute in different ways to the aggressive behavior of RA FLSs.…”

Section: Discussionmentioning

confidence: 72%

Untitled

et al. 2005

View full text Add to dashboard Cite

Fibroblast-like synoviocytes (FLSs) play a major role in the pathogenesis of rheumatoid arthritis (RA) by secreting effector molecules that promote inflammation and joint destruction. How these cells become and remain activated is still elusive. Both genetic and environmental factors probably play a role in transforming FLSs into inflammatory matrix-degrading cells. As bacterial products have been detected in the joint and shown to trigger joint inflammation, this study was undertaken to investigate whether a bacterial ligand of integrin α5β1, protein I/ II, could contribute to the aggressive behavior of RA FLSs. Protein I/II is a pathogen-associated molecular pattern (PAMP) isolated from oral streptococci that have been identified in the joints of RA patients. The response of RA and osteoarthritis FLSs to protein I/II was analyzed using human cancer cDNA expression arrays. RT-PCR and pro-MMP-3 (pro-matrix metalloproteinase) assays were then performed to confirm the up-regulation of gene expression. Protein I/II modulated about 6% of all profiled genes. Three of these, those encoding IL-6, leukemia inhibitory factor, and MMP-3, showed a high expression level in all RA FLSs tested, whereas the expression of genes encoding other members of the cytokine or MMPfamily was not affected. Furthermore, the up-regulation of MMP-3 gene expression was followed by an increase of pro-MMP-3 release. The expression of interferon regulatory factor 1 and fibroblast growth factor-5 was also up-regulated, although the expression levels were lower. Only one gene, that for insulin-like growth factor binding protein-4, was down-regulated in all RA FLSs. In contrast, in osteoarthritis FLSs only one gene, that for IL-6, was modulated. These results suggest that a bacterial ligand of integrin α5β1 may contribute to the aggressive behavior of RA FLSs by inducing the release of pro-inflammatory cytokines and a cartilage-degrading enzyme, such as IL-6 and MMP-3, respectively.

show abstract

“…Pierer et al 26 investigated the effect of TLR-2 stimulation in RA and osteoarthritis synovial fibroblasts and found differences in the induction of the chemokines GCP-2 (CXCL6), RANTES (CCL5) and MCP-2 (CCL8). Kasperkovitz et al 27 demonstrated that profiles of fibroblast-like synoviocytes derived from patients with RA divide samples into two main groups and thus show the imprint of synovial tissue heterogeneity reported previously.…”

Section: Information Generated By Gene Expression Profiling In Ramentioning

confidence: 99%

Does gene expression analysis inform us in rheumatoid arthritis?

Häupl

Stuhlmüller

Grützkau³

et al. 2009

Annals of the Rheumatic Diseases

View full text Add to dashboard Cite

Transcription profiling has become a standard technology in research. It is mainly applied in the search for biomarkers to improve diagnostic and prognostic classification, to quantify disease activity and to predict or indicate response to therapy. This review will focus on rheumatoid arthritis and discuss considerations for sample selection, prerequisites for functional interpretation of data and the current status of information deduced in the field of biomarkers for the various clinical questions. In the next few years, prediction of response to treatment is the most important aim of biomarker research. With the growing number of new biological agents, there is increasing pressure to identify molecular parameters that will not only guide the therapeutic decision but also help to define the most important targets for which new biological agents should be tested in clinical studies.

show abstract

Chemokine Secretion of Rheumatoid Arthritis Synovial Fibroblasts Stimulated by Toll-Like Receptor 2 Ligands

Cited by 25 publications

References 0 publications

A novel Saa3-promoter reporter distinguishes inflammatory subtypes in experimental arthritis and human synovial fibroblasts

A novel Saa3-promoter reporter distinguishes inflammatory subtypes in experimental arthritis and human synovial fibroblasts

Untitled

Does gene expression analysis inform us in rheumatoid arthritis?

Contact Info

Product

Resources

About