Taurine chloramine inhibition of cell proliferation and cytokine production by rheumatoid arthritis fibroblast-like synoviocytes

Abstract

Objective. To examine whether taurine (Tau) or its physiologic chlorinated derivative, taurine chloramine (Tau-Cl), affects proliferation of, and proinflammatory cytokine (interleukin-6 [IL-6] and IL-8) production by, fibroblast-like synoviocytes (FLS) isolated from rheumatoid arthritis (RA) patients.Methods. FLS, isolated from the synovial tissue of 19 RA patients and cultured in vitro for 3-6 passages, were stimulated with the recombinant human cytokines IL-1␤ (1 ng/ml), tumor necrosis factor ␣ (TNF␣; 10 ng/ml), or IL-17 (10 ng/ml) in the presence of either Tau or Tau-Cl, which were added at concentrations of 50-500 M. Tau and Tau-Cl were added simultaneously with, 2 hours before, or 24 hours after the stimuli. The concentrations of IL-6 and IL-8 were determined in culture supernatants using specific enzyme-linked immunosorbent assays. Proliferation of FLS was estimated on the basis of 3 H-thymidine incorporation into the cells, which were cultured for 72 hours in the presence of recombinant human basic fibroblast growth factor (bFGF) (1 ng/ml) and Tau or Tau-Cl, which were added simultaneously at the beginning of the culture. Rheumatoid arthritis (RA) is characterized by chronic inflammation of the synovium with hyperplasia in the synovial lining cells (1). Accumulating evidence supports the opinion that fibroblast-like synoviocytes (FLS) from RA patients are active participants in synovitis. These cells predominate in pannus and are engaged both in the destructive process (by secreting enzymes that destroy nearby tissues) and in the cytokine network (for review, see ref.2). It is well known that in the joint milieu created by the presence of various cytokines (e.g., tumor necrosis factor ␣ [TNF␣], interleukin-1␤ [IL-1␤], IL-17) (2-4) and growth factors (e.g., platelet-derived growth factor [PDGF], fibroblast growth factor [FGF]) (5,6), RA FLS proliferate and secrete IL-6 and IL-8. Both IL-6 and IL-8 are thought to participate in the pathogenesis of RA.

Taurine Chloramine Inhibits Inducible Nitric Oxide Synthase and TNF-α Gene Expression in Activated Alveolar Macrophages: Decreased NF-κB Activation and IκB Kinase Activity

“…Although the detoxification of HOCl/OCI O by Tau-Cl formation has been postulated to account for the protective effects of taurine, more recent studies suggest that Tau-Cl may be a significant biological effector molecule. This is supported by reports that Tau-Cl inhibits production of NO, TNF-␣, and other proinflammatory mediators by activated cells from a variety of different tissues (1,(12)(13)(14)(15)(16)(17). However, the mechanism of Tau-Cl action has not been determined and the effects of Tau-Cl on activated alveolar macrophages have not been reported, except in preliminary form (16).…”

Fibroblast-Like Synoviocytes from Rheumatoid Arthritis Patients Express Functional IL-15 Receptor Complex: Endogenous IL-15 in Autocrine Fashion Enhances Cell Proliferation and Expression of Bcl-xL and Bcl-2

“…Synovial fibroblast cell lines were prepared from synovial samples obtained from RA patients as described previously (35). FLS were used for experiments after three to seven passages.…”

“…To determine the contribution of endogenous IL-15 in the FLS proliferation, cells were incubated with murine IgG2a (2 g/ml) in medium with 2% FCS for 24 h. Then, medium was replaced with fresh, supplemented with mouse IgG2a (0.5; 2 g/ml) or antagonist of IL-15R␣ (IL-15DM/Fc␥2a) (0.5; 2 g/ml; Ref. 36), and FLS were cultured for an additional 72 h. [ 3 H]TdR (2 Ci/ml; Amersham Pharmacia Biotech, Little Chalfont, U.K.) was added 18 h before the termination of the cell culture, and radioactivity of the samples were measured as described (35).…”

Chondroprotective Effects of Taurine in Primary Cultures of Human Articular Chondrocytes

“…Taurine was reported to promote the expression of connective tissue growth factor (CTGF) that possesses the ability to repair damaged articular cartilage (Nishida et al 2004;Yuan et al 2007). Several researches demonstrated that taurine and its derivatives could inhibit development of rheumatoid arthritis (Kontny et al 1999;Verdrengh and Tarkowski 2005;Marcinkiewicz and Kontny 2014). On the other side, taurine was found to play an important role in bone mineral density of ovariectomized rats (Kontny et al 1999;Choi and DiMarco 2009).…”

“…Several researches demonstrated that taurine and its derivatives could inhibit development of rheumatoid arthritis (Kontny et al 1999;Verdrengh and Tarkowski 2005;Marcinkiewicz and Kontny 2014). On the other side, taurine was found to play an important role in bone mineral density of ovariectomized rats (Kontny et al 1999;Choi and DiMarco 2009). All lines of evidence suggest that taurine may affect cartilage growth.…”