Augmented interleukin‐1 production and hla–dr expression in the synovium of rheumatoid arthritis patients

Miyasaka, Nobuyuki; Sato, Kazuto; Goto, Makoto; Sasano, Minoru; Natsuyama, Motonobu; Inoue, Kazuhiko; Nishioka, Kusuki

doi:10.1002/art.1780310404

Cited by 205 publications

(70 citation statements)

References 27 publications

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“…These data indicated that CIA mice display marked upregulation of IL-1b in joints accompanied by synovial growth similar to human RA. 1,2,4 Intramuscular gene therapy using IL-1Ra DNA inhibits CIA in mice As a plasmid expression vector for intramuscular gene therapy, we used pCK, which has been shown to drive a high level of gene expression in the skeletal and cardiac muscles of mice. 22,23 The human IL-1Ra coding sequence was cloned to pCK, resulting in pCK-IL-1Ra (Figure 2a).…”

Section: Resultsmentioning

confidence: 99%

“…1 Although the causes of RA are not fully understood, various experimental and clinical studies suggest that proinflammatory cytokines, particularly interleukin-1 (IL-1) among others, have an important role in RA pathogenesis. [2][3][4][5] The IL-1 receptor antagonist (IL-1Ra) is a natural protein that competitively inhibits the binding of IL-1b and IL-1a to IL-1 receptor types I and II in humans and various animals, and improves the inflammatory symptoms of arthritis in experimental animal models. 1,[6][7][8][9][10] Several independent clinical trials have been completed in which the recombinant IL-1Ra protein has been administered for a long-term period to patients with RA.…”

Section: Introductionmentioning

confidence: 99%

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Protection against collagen-induced arthritis by intramuscular gene therapy with an expression plasmid for the interleukin-1 receptor antagonist

Jeong

et al. 2003

Gene Ther

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The interleukin-1 receptor antagonist (IL-1Ra) is an endogenous protein that can prevent the binding of IL-1 to its cellsurface receptors. Among a number of techniques for gene transfer in vivo, the direct injection of naked DNA into muscle is simple, inexpensive and safe. In this study, we evaluated the potential of intramuscular gene therapy with plasmid DNA containing the cDNA for IL-1Ra in the prevention of murine collagen-induced arthritis (CIA). DBA/1 mice were immunized with bovine type II collagen. At 4 weeks after the initial immunization, expression plasmid for IL-1Ra was injected into four selected sites in the thigh and calf muscles of DBA/1 mice. Control mice received the same plasmid, but lacking the IL-1Ra coding sequence. Macroscopic analysis of paws for redness, swelling and deformities showed that the onset of moderate to severe CIA in the paws of mice injected with IL-1Ra DNA was significantly prevented (Po0.05). In addition, both the synovitis and the cartilage erosion in knee joints were dramatically reduced in mice treated with IL-1Ra DNA (Po0.05). The expression of IL-1b was significantly decreased in the ankle joints of mice treated with IL-1Ra (Po0.01). Interestingly, the levels of IL-1Ra in sera and joints after intramuscular injection of IL-1Ra DNA were significantly lower than when protein had been used in previous reports, suggesting that the therapeutic effect may be achieved by an alternative mechanism(s) rather than by systemic elevation of IL-1Ra. These observations provide the first evidence that direct intramuscular injection of expression plasmid for IL-1Ra may effectively suppress the inflammatory pathology in arthritis.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Protection against collagen-induced arthritis by intramuscular gene therapy with an expression plasmid for the interleukin-1 receptor antagonist

Jeong

et al. 2003

Gene Ther

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“…Synovial cells from an RA patient were obtained during total knee replacement, as described elsewhere (9). Binding experiments were performed as previously described (10).…”

Section: Methodsmentioning

confidence: 99%

Increased production of endothelin‐1 in patients with inflammatory arthritides

Miyasaka

Hirata

Ando

et al. 1992

Arthritis & Rheumatism

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Objective. Endothelin-1 (ET-1) is a potent vasoconstrictive peptide, but its precise mechanism of action in vivo has remained unknown.Methods. We measured ET-1 activity by radioimmunoassay, in both plasma and synovial fluid from patients with inflammatory arthritides.Results. ET-1-like immunoreactivity was found in synovial fluid, at levels severalfold higher than those in plasma. Reverse-phase high-performance liquid chromatography showed an elution profile corresponding to actual ET-1. A single class of high-atfinity binding sites for ET-1 in cultured synovial cells was also detected. Conclusion. Taken together, these results indicate that ET-1 might contribute to the synovial proliferation seen in inflammatory arthritides, in an autocrine/paracrine manner.Endothelin-I (ET-I), a 21-amino acid polypeptide with 2 intramolecular disulfide bonds, induces potent, sustained vasoconstriction in vitro and longlasting elevation of blood pressure in vivo (1). It also stimulates in vitro proliferation of mesangial cells, fibroblasts, and vascular smooth muscle cells (2-4). Endothelin production in endothelial cells is augmented by thrombin, transforming growth factor P (TGFP), and interleukin-l (5,6), some of which are known to be up-regulated in rheumatoid arthritis (RA). We therefore hypothesized that endothelin might be produced locally in the joints of patients with inflammatory arthritides. In the present study, we investigated this hypothesis and examined the possible role of endothelin in joint destruction. PATIENTS AND METHODSPatients. Twenty-three patients (18 women, 5 men; ages 39-82 years) who fulfilled the American College of Rheumatology (formerly, the American Rheumatism Association) criteria for RA (7), 11 patients (9 women, 2 men; ages 54-76 years) with osteoarthritis (OA) (5 of whom had inflammatory effusions in the knee), and 18 patients (all men; ages 34-58 years) with gout (4 of whom had acute knee arthritis with effusions) were entered into the study. Patients who were taking more than 5 mglday of prednisolone andlor 100 mglday of D-penicillamine were excluded from the study. RA patients were assigned to active or inactive

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“…Furthermore, preliminary experiments reveal the presence of IL-1 and IL-6 activities in culture supernatants of synovial tissues and SF cells from patients with this arthropathy; which cells are responsible for the production of these cytokines is still unknown. We have already reported that IL-1 and IL-6 productions are augmented by the proliferating synovial tissue in RA and other inflammatory arthropathies (13,14). These findings suggest that cytokines, including IL-1, IL-6, and other factors, might be produced by the HTLV-I-infected cells themselves or as a result of the immune reaction to HTLV-I infection in the synovium.…”

Section: Discussionmentioning

confidence: 80%

“…Immunohistochemical staining was performed using a modification of the method described previously (13,14). Briefly, frozen sections or smears were air-dried and fixed with cold acetone for 10 minutes.…”

Section: Methodsmentioning

confidence: 99%

Arthritis in patients infected with human T lymphotropic virus type I. Clinical and immunopathologic features

Sato

Maruyama

et al. 1991

Arthritis & Rheumatism

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Ten patients with chronic inflammatory arthropathy and the human T lymphotropic virus type I (HTLV-I) are described. These patients showed chronic persistent oligoarthritis, associated with proliferative synovitis, in large joints. The place of birth or residence of these patients was within the area endemic for adult T cell leukemia (ATL) and HTLV-I. The age at onset of articular symptoms tended to be higher in these patients than in typical rheumatoid arthritis patients. Anti-HTLV-I antibodies were detected in both sera and synovial fluids from all patients. Western blot analysis revealed antibodies to viral gag proteins (p19, p24, and p28). Atypical lymphocytes with nuclear indentations, consistent with ATL-like cells, were observed in both synovial fluid and synovial tissue. Furthermore, HTLV-I proviral DNA was integrated into the DNA of

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Augmented interleukin‐1 production and hla–dr expression in the synovium of rheumatoid arthritis patients

Cited by 205 publications

References 27 publications

Protection against collagen-induced arthritis by intramuscular gene therapy with an expression plasmid for the interleukin-1 receptor antagonist

Protection against collagen-induced arthritis by intramuscular gene therapy with an expression plasmid for the interleukin-1 receptor antagonist

Increased production of endothelin‐1 in patients with inflammatory arthritides

Arthritis in patients infected with human T lymphotropic virus type I. Clinical and immunopathologic features

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