Synovial cells

Rheumatoid synovial cells produce a broad range of cytokines (Brennan et al., 1991). The formation of IL-la, IL-1 /3, GM-CSF, G-CSF, TNFa and other cytokines may be under the direct influence of ox-LDL and/or... 

Hakala BE, White C, Recklies AD 1993 Human cartilage gp-39, a major secretory product of articular chondrocytes and synovial cells, is a mammalian member of a chitinase protein family. J Biol Chem 268 25803-25810... 

GM-CSF is undetectable in the serum of normal humans, and no normal cells have been shown to express this protein constitutively. Some transformed cells may constitutively express GM-CSF, and it is actively synthesised and secreted by antigen- and lectin-stimulated T cells and by endothelial cells and fibroblasts exposed to TNF, IL-1 or endotoxin. Other sources of GM-CSF include stimulated B lymphocytes, macrophages, mast cells and osteoblasts, whilst TNF and IL-1 can stimulate its production by acute myeloid leukaemia cells. Some solid tumours and synovial cells from rheumatoid joints may also express GM-CSF and this may be important in disease pathology. 

ICAM-1 and -2 are constitutively expressed on endothelial cells ICAM-1 may be further up-regulated by exposure to cytokines. ICAM-3 has recently been described (its identity based on the unique specificity of a monoclonal antibody) and is a 124-kDa glycoprotein present on the surfaces of T cells, monocytes and neutrophils its expression may be up-regulated by stimulants such as mitogens. VCAM-1, which is expressed on the luminal surface of cytokine-exposed endothelial cells, binds T cells via VLA-4. It is also expressed on the surface of some leukaemic cell lines, on rheumatoid synovial cells and on some tumours.On the other hand, ICAM-1 is found on all endothelial surfaces, and its interaction with neutrophil integrins is the major mechanism that results in the stimulation of transendothelial migration. 

Alvaro-Gracia, J. M., Zvaifler, N. J., Brown, C. B., Kaushansky, K., Firestein, G. S. (1991). Cytokines in chronic inflammatory arthritis VI. Analysis of the synovial cells involved in granulocyte-macrophage colony-stimulating factor production and gene expression in rheumatoid arthritis and its regulation by IL-1 and tumor necrosis factor-a J. Immunol 146,3365-71. 

Brennan, F. M., Zachariae, C. O. C., Chantry, D., Larsen, C. G., Turner, M., Maini, R. N., Matsushima, K., Feldmann, M. (1990). Detection of Interleukin 8 biological activity in synovial fluids from patients with rheumatoid arthritis and production of Interleukin 8 mRNA by isolated synovial cells. Eur. J. Immunol. 20,2141-4. 

Perotti M, Toddei F, Mirabelli F. Vairetti M, Bellomo G, McConkey DJ, Orrenius S (1990) Calcium-dependent DNA fragmentation in human synovial cells exposed to cold shock. FEES Lett 259 331-334... 

Kawai, S., Nishida, S., Kato, M., Furumaya, Y., Okamoto, R., Koshino, T, Mizushima, Y. Comparison of cyclooxygenase-1 and -2 inhibitory activities of various nonsteroidal anti-inflammatory drugs using human platelets and synovial cells, Eur. J. Pharmacol. 1998, 347, 87-94. 

Goldberg RL, Kaplan SR, Fuller GC. 1983. Effect of heavy metals on human rheumatoid synovial cell proliferation and collagen synthesis. Biochem Pharmacol 32 2763-2766. 

Yamazaki R., Kusunoki N., Matsuzaki T., Hashimoto S., and Kawai S. (2002). Nonsteroidal antiinflammatory drugs induce apoptosis in association with activation of peroxisome proliferator-activated receptor y in rheumatoid synovial cells. J. Pharmacol. Exp. Ther. 302 18-25. 

Yovandich, J., O Malley, B., Sikes, M. and Ledley, F.D. (1995) Gene transfer to synovial cells by intra-articular administration of plasmid DNA. Hum. Gene Ther., 6, 603-610. 

Morand, E.F., Hall, P., Hutchinson, P., and Y.H. Yang, 2006, Regulation of annexin I in rheumatoid synovial cells by glucocorticoids and interleukin-1. Mediators Inflamm. (2) 73835. 

Grandolfo M, Calabrese A, D Andrea P. Mechanism of mechanically induced intercellular calcium waves in rabbit articular chondrocytes and in HIG-82 synovial cells. / Bone Miner Res. 1998 13 443-453. 

Al is also present in the synovial fluid and arthritis-like symptoms have been reported in patients with Al bone disease, possibly due to an inflammatory effect on the synovial cells [107, 108]. We did not see signs of arthritis shortly after the intoxication, but after several months of treatment with desferrioxamine, three patients developed a possible transient synovitis with hydrops in the knee joints. 

In later TEM studies by Ghadially et al. (48), a lower concentration of cisplatin (30 (xM) was incubated in HeLa and human lymphoblastoid (RPMI 6410) cells for periods that ranged from 1 hour to 4 days. No intracellular platinum was detected in either cell line. However, similar incubations with platinum(II)-uracil resulted in development of lysosome-like bodies in the cytosol, which are referred to as platinosomes, that contain electron dense species identified by X-ray analysis as platinum (48). In a related study, similar concentrations of cisplatin were injected into rabbit knee joints and incubated for several days. Again, no platinum was detected in the intracellular or extracellular compartments of the synovial cells, whereas platinum was observed to accumulate only in the platinosomes after platinum-uracil incubation (49). This set of studies highlights the effect of incubation concentrations of the drug on the cellular distribution results, as well as, drawing attention to the uptake of some platinum(II) complexes in cytoplasmic organelles. 

Yai on I, Shirazi I, Judovich R, Levartovsky D, Caspi D, Yar on M (19 99) Fluoxetine and amitriptyline inlribit nitric oxide, prostaglandin E2, and hyalui onic acid production in human synovial cells and synovial tissue cultui es. Ai tlriitis Rlreum 42 2561—2568. 

May S A, Hooke R E, Lees P 1988 The effect of drugs used in the treatment of osteoarthrosis on stromelysin (proteoglycanase) of equine synovial cell origin. Equine Veterinary Journal Supplement 25 28-32... 

Recklles A D, White C, Melching L et al 2001 Differential regulation and expression of hyaluronan synthases in human articular chondrocytes, synovial cells and osteosarcoma cells. Biochemical Journal 354 17-24... 

Takeshita S, Mizuno S, Kikuchi T et al 1997 The in vitro effect of hyaiuronic acid on IL-1-beta production in cultured rheumatoid synovial cells. Biomedical Research rtokyo) 18 187-194... 

Dayer, J.M., Beutler, B. and Cerami, A. (1985). Cachectin/ tumor necrosis Eiaor stimulates collagenase and prostaglandin E2 production by human synovial cells and dermal fibroblasts. J. Exp. Med. 162, 2163-2168. 

Yoffe, J., Taylor, D.J. and Woolley, D.E. (1980 Mast cell products stimulate collagenase and prostaglandin E production by cultures of adherent rheumatoid synovial cells. Biochem. Biophys. Res. Commun. 122, 270-276. 

It was a very important discovery made by Clarris and Fraser that some cells (e.g. synovial cells) are covered by a hyaluronidase-sensitive coat [80]. Accordingly, different cell lines have variable ability to S5mthesize HA. 

Leflunomide (Arava) is an anti-inflammatory medication used to treat the symptoms of RA. Leflunomide suppresses HA release from the synovial cells that line the joint capsule in a dose-dependent marmer [130]. Leflunomide specifically suppresses induction of HASl. HAS2 and HAS3, which are constitutively expressed in synovial cells, are not affected. Leflunomide is a specific NF-kB inhibitor, but does not affect HASl in this manner. Rather, leflunomide functions here by suppressing t5o-osine kinases. 

Organic and aqueous feverfew powdered leaf extracts were found to inhibit IL-1-induced prostaglandin E2 release from synovial cells, IL-2-induced thymidine uptake by lymphoblasts, and mitogen-induced uptake of thymidine by peripheral blood mononuclear cells (PBMCs) (23). Parthenolide also inhibited thymidine uptake by PBMCs. Both parthenolide and the extracts were cytotoxic to the PBMCs and synovial cells thus, the anti-inflammatory effects of feverfew may be secondary to cytotoxicity. These results reflect those of previous researchers who found parthenolide and other sesquiterpene lactones to be cytotoxic to cultures of human fibroblasts, human laryngeal carcinoma cells, and human cells transformed with simian virus 40 (24). 

Dayer J-M, Beutler B, Cerami A. 1985. Cachectin/tumor necrosis factor (TNF) stimulates collagenase and PGE2 production by human synovial cells and der-... 

TNF-stimulated gene 6 (TSG-6), encoding a 35kDa secretory glycoprotein (TSG-6), is induced in fibroblasts, chondrocytes, synovial cells, and mononuclear cells by the... 

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