title: Transforming Growth Factor-β1 and Laminin-111 Cooperate in the Regulation of Expression of Interleukin-6 and Interleukin-8 in Synovial Fibroblasts.
abstract: 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.
authors.affiliation: Center for Regenerative Biology and Medicine (ZRM), Center for Medical Research, University of Tübingen Medical School, Tübingen, Germany;
authors.forename: Tino
authors.initials: T
authors.lastname: Felka
authors.forename: Katrin
authors.initials: K
authors.lastname: Warstat
authors.forename: Torsten
authors.initials: T
authors.lastname: Kluba
authors.forename: Falk
authors.initials: F
authors.lastname: Mittag
authors.forename: Maik
authors.initials: M
authors.lastname: Hoberg
authors.forename: Gerd
authors.initials: G
authors.lastname: Klein
authors.forename: Wilhelm K
authors.initials: WK
authors.lastname: Aicher
keywords: IL-6; IL-8; TGF-β synovial fibroblast; arthritis; inflammation