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author:("homberg, Maik")
1.  Transforming Growth Factor-β1 and Laminin-111 Cooperate in the Regulation of Expression of Interleukin-6 and Interleukin-8 in Synovial Fibroblasts 
In a recent study we showed that binding of synovial fibroblasts (SF) to laminin-111 (LM-111) in the presence of TGF-β1 induced a significant production of IL-16. Here we go on to investigate the regulation of IL-6 and IL-8 in SF by LM-111 and TGF-β1. Changes in steady state mRNA levels encoding the interleukins were investigated by quantitative RT-PCR. We screened for interleukin production by a multiplexed immunoarray and quantified it with ELISA. The biological activity of IL-6 and IL-8 was corroborated by B-lymphocyte proliferation and cell migration assays, respectively. Growth of SF on LM-111 in presence of TGF-β1 induced significant mRNA responses for IL-6 (mean 3.72-fold increase, ± 1.6, p<0.003) and IL-8 (mean 4.5-fold increase, ± 1.6, p<0.001). In the supernatants significantly elevated concentrations of IL-6 (mean 7.9 ± 5 ng/mL, p<0.005) and IL-8 (mean 73.0 ng/mL ± 51, p<0.05) were detected, and they were shown to be biologically active. Binding to LM-111 in the presence of TGF-β1 activates SF for expression of IL-6 and IL-8 and thus may contribute to synovial inflammation and to infiltration of leukocytes.
PMCID: PMC3615287  PMID: 23675204
arthritis; inflammation; IL-6; IL-8; TGF-β synovial fibroblast
2.  Attachment to laminin‐111 facilitates transforming growth factor β‐induced expression of matrix metalloproteinase‐3 in synovial fibroblasts 
Annals of the Rheumatic Diseases  2006;66(4):446-451.
Background
In the synovial membrane of patients with rheumatoid arthritis (RA), a strong expression of laminins and matrix degrading proteases was reported.
Aim
To investigate the regulation of matrix metalloproteinases (MMPs) in synovial fibroblasts (SFs) of patients with osteoarthritis (OA) and RA by attachment to laminin‐1 (LM‐111) and in the presence or absence of costimulatory signals provided by transforming growth factor β (TGFβ).
Methods
SFs were seeded in laminin‐coated flasks and activated by addition of TGFβ. The expression of genes was investigated by quantitative reverse transcriptase‐polymerase chain reaction (qRT‐PCR), immunocytochemistry and ELISA, and intracellular signalling pathways by immunoblotting, and by poisoning p38MAPK by SB203580, MEK‐ERK by PD98059 and SMAD2 by A‐83‐01.
Results
Attachment of SF to LM‐111 did not activate the expression of MMPs, but addition of TGFβ induced a fivefold higher expression of MMP‐3. Incubation of SF on LM‐111 in the presence of TGFβ induced a significant 12‐fold higher expression of MMP‐3 mRNA, and secretion of MMP‐3 was elevated 20‐fold above controls. Functional blocking of LM‐111–integrin interaction reduced the laminin‐activated MMP‐3 expression significantly. Stimulation of SF by LM‐111 and TGFβ activated the p38MAPK, ERK and SMAD2 pathways, and inhibition of these pathways by using SB203580, PD98059 or A‐83‐01 confirmed the involvement of these pathways in the regulation of MMP‐3.
Conclusion
Attachment of SF to LM‐111 by itself has only minor effects on the expression of MMP‐1 or MMP‐3, but it facilitates the TGFβ‐induced expression of MMP‐3 significantly. This mode of MMP‐3 induction may therefore contribute to inflammatory joint destruction in RA independent of the proinflammatory cytokines interleukin (IL)1β or tumour necrosis factor (TNF)α.
doi:10.1136/ard.2006.060228
PMCID: PMC1856036  PMID: 17124250

Results 1-2 (2)