The Experts below are selected from a list of 273 Experts worldwide ranked by ideXlab platform
Takahiko Aoyagi - One of the best experts on this subject based on the ideXlab platform.
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Nitric oxide protects cultured rheumatoid Synovial Cells from Fas-induced apoptosis by inhibiting caspase-3.
Immunology, 2001Co-Authors: Kiyoshi Migita, Satoshi Yamasaki, Hiroaki Ida, Takahiko Aoyagi, Masako Kita, Kazutaka Shibatomi, Atsushi Kawakami, Katsuni EguchiAbstract:Nitric oxide (NO) is elevated in the Synovial fluids and sera of patients with rheumatoid arthritis (RA) and is thought to be an important proinflammatory mediator in the rheumatoid synovium. To test the hypothesis that NO might modulate the apoptosis-inducing signal pathway, we investigated the effects of NO on rheumatoid Synovial-Cell apoptosis induced by Fas ligation with anti-Fas antibody. Pretreatment of Synovial Cells with the NO donor S-nitro-N-acetylpenicillamine (SNAP) prevented the Fas-mediated induction of apoptosis. The activation of caspase-3 was required to mediate Fas-induced Synovial Cell apoptosis. The NO donor SNAP inhibited Fas-induced caspase-3 activation in rheumatoid Synovial Cells. However, NO did not interrupt Fas-induced caspase-8 cleavage or subsequent cytochrome c release into the cytosol in rheumatoid Synovial Cells. These data indicate that NO prevents apoptosis in rheumatoid Synovial Cells by directly inhibiting caspase-3 activation. Thus, we propose that NO interferes with Cell death signal transduction and may contribute to rheumatoid Synovial Cell proliferation by inhibiting induction of apoptosis.
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Regulation of Rheumatoid Synovial Cell Growth by Ceramide
Biochemical and biophysical research communications, 2000Co-Authors: Kiyoshi Migita, Satoshi Yamasaki, Hiroaki Ida, Takahiko Aoyagi, Masako Kita, Seiyo Honda, Yasuko Hirai, Takaaki Fukuda, Toshiaki Tsukada, Atsushi KawakamiAbstract:Overgrowth of rheumatoid synoviocytes, which results in joint destruction, is due to impaired balance between Cell proliferation and Cell death (apoptosis). Ceramide is an important lipid messenger involved in mediating a variety of Cell functions including apoptosis. We investigated the effects of ceramide on growth-promoting anti-apoptotic signals in rheumatoid Synovial Cells. Human Synovial Cells isolated from patients with rheumatoid arthritis (RA) were stimulated with platelet-derived growth factor (PDGF) in the presence or absence of C2-ceramide. The kinase activity of Akt, MEK, and ERK1/2 was analyzed in PDGF-stimulated Synovial Cells by Western blot analysis. Pretreatment with C2-ceramide completely inhibited PDGF-induced Cell cycle progression of rheumatoid Synovial Cells. PDGF stimulation induced phosphorylation and activation of Akt, MEK, and ERK1/2 in rheumatoid Synovial Cells. C2-ceramide inhibited the activation of Akt, MEK and ERK1/2 in PDGF-stimulated Synovial Cells. Our data demonstrated that inhibition of anti-apoptotic kinases, such as Akt and ERK1/2, may play an important role in ceramide-mediated apoptosis of rheumatoid Synovial Cells.
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Regulation of Synovial Cell apoptosis by proteasome inhibitor.
Arthritis and rheumatism, 1999Co-Authors: Atsushi Kawakami, Satoshi Yamasaki, Hiroaki Ida, Tomoki Nakashima, Hideaki Sakai, Ayumi Hida, Satoshi Urayama, Hideki Nakamura, Yasufumi Ichinose, Takahiko AoyagiAbstract:Objective. Recent studies have shown the importance of proteasome function in the regulation of apoptosis. This study examined whether inhibition of proteasome function mediates apoptosis of Synovial Cells, and whether cytokines modulate this process. Methods. Type B Synovial Cells (fibroblast-like Synovial Cells) were cultured with tumor necrosis factor a (TNFa) or transforming growth factor b1 (TGFb1), and further incubated in the presence of variable concentrations of Z-Leu-Leu-Leu-aldehyde (LLL-CHO), a proteasome inhibitor. During this process, apoptosis of Synovial Cells was determined by Hoechst 33258 dye staining and 51 Cr release assay. The involvement of caspase cascade was examined using enzyme activity assay and blocking experiments by peptide inhibitors. The expression of pro-caspases, Bcl-2‐related proteins, and X chromosome‐linked inhibitor of apoptosis (XIAP) in Synovial Cells was examined by Western blot analysis. Results. Apoptosis of cultured Synovial Cells was induced in a dose-dependent manner by LLL-CHO. Activation of caspase cascade through caspase-8 to caspase-3 was essential during this process. Pretreatment of Synovial Cells with TNFa significantly augmented both the activation of caspases and the proportion of apoptosis in Synovial Cells induced by LLL-CHO, whereas TGFb1 pretreatment markedly suppressed these phenomena. The ratio of the expression of Bcl-2 to Bax or Bcl-xL to Bax, and XIAP expression in Synovial Cells may not be directly associated with the susceptibility of Synovial Cells to apoptosis by LLL-CHO. Conclusion. Apoptosis of Synovial Cells was induced by inhibition of proteasome function through the activation of caspase cascade, and this process was clearly modulated by cytokines. These data provide new insight into the regulatory mechanisms controlling Synovial Cells in rheumatoid synovitis by proteasome inhibitors, and might be useful for the design of new therapeutic strategies in rheumatoid arthritis.
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Interleukin 4 increases human Synovial Cell expression of VCAM-1 and T Cell binding.
Annals of the rheumatic diseases, 1994Co-Authors: H Shimada, K. Eguchi, Yukitaka Ueki, Munetoshi Nakashima, I Yamashita, Yojiro Kawabe, M Sakai, Hiroaki Ida, Takahiko Aoyagi, S. NagatakiAbstract:OBJECTIVE--The effects were studied of interleukin 4 (IL-4) on T Cell-Synovial Cell adhesion and on the expression of adhesion molecules on the surface of Synovial fibroblast-like Cells. METHODS--The adhesion of T Cells toward the Synovial Cells were measured by 51chromium-labelled adhesion assay. The expression of adhesion molecules on Synovial Cells were analysed by flowcytometry. RESULTS--Stimulation of Synovial Cells with IL-4 increased T Cell-Synovial Cells adhesion in a time- and dose-dependent manner. IL-4 considerably enhanced the expression of VCAM-1 on the surface of Synovial Cells, but not the expression of ICAM-1 and ELAM-1. The combination of IL-1 beta and IL-4 had no effect on the expression of ICAM-1 or VCAM-1 on the surface of Synovial Cells. The increased adhesion of T Cells to IL-4 stimulated Synovial Cells was inhibited significantly by adding anti-VCAM-1 or anti-CD29 monoclonal antibody. Furthermore, anti-VLA-4 alpha or the combination of anti-VLA-4 alpha and anti-VCAM-1 antibodies blocked completely T-Cell binding to IL-4 stimulated Synovial Cells. CONCLUSIONS--These results suggest that the increased adhesion of T Cells to IL-4-stimulated Synovial Cells is mediated by VLA-4/VCAM-1 pathway.
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Infection of human Synovial Cells by human T Cell lymphotropic virus type I. Proliferation and granulocyte/macrophage colony-stimulating factor production by Synovial Cells.
The Journal of clinical investigation, 1993Co-Authors: M Sakai, Munetoshi Nakashima, I Yamashita, Yojiro Kawabe, Hiroaki Ida, Takahiko Aoyagi, Katsumi Eguchi, Kaoru Terada, H Takino, T NakamuraAbstract:The present study was performed to clarify the relationship between human T Cell lymphotropic virus type I (HTLV-I) infection and chronic inflammatory arthropathy. To determine the ability of HTLV-I to infect Synovial Cells and the effect on Synovial Cell proliferation, Synovial Cells were cocultured with the HTLV-I-producing T Cell lines (MT-2 or HCT-1). After coculture with HTLV-I-infected T Cells, the Synovial Cells expressed HTLV-I-specific core antigens, and HTLV-I proviral DNA was detected from the Synovial Cells by polymerase chain reaction. These cocultured Synovial Cells with HTLV-I-infected T Cells proliferated more actively than the Synovial Cells cocultured with uninfected T Cells. This stimulatory effect of HTLV-I-infected T Cells on Synovial Cell proliferation seems necessary to contact each other. After being cocultured with MT-2 Cells, Synovial Cells proliferated more actively than control Cells even after several passages. Furthermore, HTLV-I-infected Synovial Cells produced significant amounts of granulocyte/macrophage colony-stimulating factor. These results suggest that HTLV-I can infect Synovial Cells, resulting their active proliferation and may be involved in the pathogenesis of proliferative synovitis similar to that found in rheumatoid arthritis.
Hiroaki Ida - One of the best experts on this subject based on the ideXlab platform.
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Nitric oxide protects cultured rheumatoid Synovial Cells from Fas-induced apoptosis by inhibiting caspase-3.
Immunology, 2001Co-Authors: Kiyoshi Migita, Satoshi Yamasaki, Hiroaki Ida, Takahiko Aoyagi, Masako Kita, Kazutaka Shibatomi, Atsushi Kawakami, Katsuni EguchiAbstract:Nitric oxide (NO) is elevated in the Synovial fluids and sera of patients with rheumatoid arthritis (RA) and is thought to be an important proinflammatory mediator in the rheumatoid synovium. To test the hypothesis that NO might modulate the apoptosis-inducing signal pathway, we investigated the effects of NO on rheumatoid Synovial-Cell apoptosis induced by Fas ligation with anti-Fas antibody. Pretreatment of Synovial Cells with the NO donor S-nitro-N-acetylpenicillamine (SNAP) prevented the Fas-mediated induction of apoptosis. The activation of caspase-3 was required to mediate Fas-induced Synovial Cell apoptosis. The NO donor SNAP inhibited Fas-induced caspase-3 activation in rheumatoid Synovial Cells. However, NO did not interrupt Fas-induced caspase-8 cleavage or subsequent cytochrome c release into the cytosol in rheumatoid Synovial Cells. These data indicate that NO prevents apoptosis in rheumatoid Synovial Cells by directly inhibiting caspase-3 activation. Thus, we propose that NO interferes with Cell death signal transduction and may contribute to rheumatoid Synovial Cell proliferation by inhibiting induction of apoptosis.
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Regulation of Rheumatoid Synovial Cell Growth by Ceramide
Biochemical and biophysical research communications, 2000Co-Authors: Kiyoshi Migita, Satoshi Yamasaki, Hiroaki Ida, Takahiko Aoyagi, Masako Kita, Seiyo Honda, Yasuko Hirai, Takaaki Fukuda, Toshiaki Tsukada, Atsushi KawakamiAbstract:Overgrowth of rheumatoid synoviocytes, which results in joint destruction, is due to impaired balance between Cell proliferation and Cell death (apoptosis). Ceramide is an important lipid messenger involved in mediating a variety of Cell functions including apoptosis. We investigated the effects of ceramide on growth-promoting anti-apoptotic signals in rheumatoid Synovial Cells. Human Synovial Cells isolated from patients with rheumatoid arthritis (RA) were stimulated with platelet-derived growth factor (PDGF) in the presence or absence of C2-ceramide. The kinase activity of Akt, MEK, and ERK1/2 was analyzed in PDGF-stimulated Synovial Cells by Western blot analysis. Pretreatment with C2-ceramide completely inhibited PDGF-induced Cell cycle progression of rheumatoid Synovial Cells. PDGF stimulation induced phosphorylation and activation of Akt, MEK, and ERK1/2 in rheumatoid Synovial Cells. C2-ceramide inhibited the activation of Akt, MEK and ERK1/2 in PDGF-stimulated Synovial Cells. Our data demonstrated that inhibition of anti-apoptotic kinases, such as Akt and ERK1/2, may play an important role in ceramide-mediated apoptosis of rheumatoid Synovial Cells.
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Regulation of Synovial Cell apoptosis by proteasome inhibitor.
Arthritis and rheumatism, 1999Co-Authors: Atsushi Kawakami, Satoshi Yamasaki, Hiroaki Ida, Tomoki Nakashima, Hideaki Sakai, Ayumi Hida, Satoshi Urayama, Hideki Nakamura, Yasufumi Ichinose, Takahiko AoyagiAbstract:Objective. Recent studies have shown the importance of proteasome function in the regulation of apoptosis. This study examined whether inhibition of proteasome function mediates apoptosis of Synovial Cells, and whether cytokines modulate this process. Methods. Type B Synovial Cells (fibroblast-like Synovial Cells) were cultured with tumor necrosis factor a (TNFa) or transforming growth factor b1 (TGFb1), and further incubated in the presence of variable concentrations of Z-Leu-Leu-Leu-aldehyde (LLL-CHO), a proteasome inhibitor. During this process, apoptosis of Synovial Cells was determined by Hoechst 33258 dye staining and 51 Cr release assay. The involvement of caspase cascade was examined using enzyme activity assay and blocking experiments by peptide inhibitors. The expression of pro-caspases, Bcl-2‐related proteins, and X chromosome‐linked inhibitor of apoptosis (XIAP) in Synovial Cells was examined by Western blot analysis. Results. Apoptosis of cultured Synovial Cells was induced in a dose-dependent manner by LLL-CHO. Activation of caspase cascade through caspase-8 to caspase-3 was essential during this process. Pretreatment of Synovial Cells with TNFa significantly augmented both the activation of caspases and the proportion of apoptosis in Synovial Cells induced by LLL-CHO, whereas TGFb1 pretreatment markedly suppressed these phenomena. The ratio of the expression of Bcl-2 to Bax or Bcl-xL to Bax, and XIAP expression in Synovial Cells may not be directly associated with the susceptibility of Synovial Cells to apoptosis by LLL-CHO. Conclusion. Apoptosis of Synovial Cells was induced by inhibition of proteasome function through the activation of caspase cascade, and this process was clearly modulated by cytokines. These data provide new insight into the regulatory mechanisms controlling Synovial Cells in rheumatoid synovitis by proteasome inhibitors, and might be useful for the design of new therapeutic strategies in rheumatoid arthritis.
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Interleukin 4 increases human Synovial Cell expression of VCAM-1 and T Cell binding.
Annals of the rheumatic diseases, 1994Co-Authors: H Shimada, K. Eguchi, Yukitaka Ueki, Munetoshi Nakashima, I Yamashita, Yojiro Kawabe, M Sakai, Hiroaki Ida, Takahiko Aoyagi, S. NagatakiAbstract:OBJECTIVE--The effects were studied of interleukin 4 (IL-4) on T Cell-Synovial Cell adhesion and on the expression of adhesion molecules on the surface of Synovial fibroblast-like Cells. METHODS--The adhesion of T Cells toward the Synovial Cells were measured by 51chromium-labelled adhesion assay. The expression of adhesion molecules on Synovial Cells were analysed by flowcytometry. RESULTS--Stimulation of Synovial Cells with IL-4 increased T Cell-Synovial Cells adhesion in a time- and dose-dependent manner. IL-4 considerably enhanced the expression of VCAM-1 on the surface of Synovial Cells, but not the expression of ICAM-1 and ELAM-1. The combination of IL-1 beta and IL-4 had no effect on the expression of ICAM-1 or VCAM-1 on the surface of Synovial Cells. The increased adhesion of T Cells to IL-4 stimulated Synovial Cells was inhibited significantly by adding anti-VCAM-1 or anti-CD29 monoclonal antibody. Furthermore, anti-VLA-4 alpha or the combination of anti-VLA-4 alpha and anti-VCAM-1 antibodies blocked completely T-Cell binding to IL-4 stimulated Synovial Cells. CONCLUSIONS--These results suggest that the increased adhesion of T Cells to IL-4-stimulated Synovial Cells is mediated by VLA-4/VCAM-1 pathway.
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Infection of human Synovial Cells by human T Cell lymphotropic virus type I. Proliferation and granulocyte/macrophage colony-stimulating factor production by Synovial Cells.
The Journal of clinical investigation, 1993Co-Authors: M Sakai, Munetoshi Nakashima, I Yamashita, Yojiro Kawabe, Hiroaki Ida, Takahiko Aoyagi, Katsumi Eguchi, Kaoru Terada, H Takino, T NakamuraAbstract:The present study was performed to clarify the relationship between human T Cell lymphotropic virus type I (HTLV-I) infection and chronic inflammatory arthropathy. To determine the ability of HTLV-I to infect Synovial Cells and the effect on Synovial Cell proliferation, Synovial Cells were cocultured with the HTLV-I-producing T Cell lines (MT-2 or HCT-1). After coculture with HTLV-I-infected T Cells, the Synovial Cells expressed HTLV-I-specific core antigens, and HTLV-I proviral DNA was detected from the Synovial Cells by polymerase chain reaction. These cocultured Synovial Cells with HTLV-I-infected T Cells proliferated more actively than the Synovial Cells cocultured with uninfected T Cells. This stimulatory effect of HTLV-I-infected T Cells on Synovial Cell proliferation seems necessary to contact each other. After being cocultured with MT-2 Cells, Synovial Cells proliferated more actively than control Cells even after several passages. Furthermore, HTLV-I-infected Synovial Cells produced significant amounts of granulocyte/macrophage colony-stimulating factor. These results suggest that HTLV-I can infect Synovial Cells, resulting their active proliferation and may be involved in the pathogenesis of proliferative synovitis similar to that found in rheumatoid arthritis.
Atsushi Kawakami - One of the best experts on this subject based on the ideXlab platform.
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Nitric oxide protects cultured rheumatoid Synovial Cells from Fas-induced apoptosis by inhibiting caspase-3.
Immunology, 2001Co-Authors: Kiyoshi Migita, Satoshi Yamasaki, Hiroaki Ida, Takahiko Aoyagi, Masako Kita, Kazutaka Shibatomi, Atsushi Kawakami, Katsuni EguchiAbstract:Nitric oxide (NO) is elevated in the Synovial fluids and sera of patients with rheumatoid arthritis (RA) and is thought to be an important proinflammatory mediator in the rheumatoid synovium. To test the hypothesis that NO might modulate the apoptosis-inducing signal pathway, we investigated the effects of NO on rheumatoid Synovial-Cell apoptosis induced by Fas ligation with anti-Fas antibody. Pretreatment of Synovial Cells with the NO donor S-nitro-N-acetylpenicillamine (SNAP) prevented the Fas-mediated induction of apoptosis. The activation of caspase-3 was required to mediate Fas-induced Synovial Cell apoptosis. The NO donor SNAP inhibited Fas-induced caspase-3 activation in rheumatoid Synovial Cells. However, NO did not interrupt Fas-induced caspase-8 cleavage or subsequent cytochrome c release into the cytosol in rheumatoid Synovial Cells. These data indicate that NO prevents apoptosis in rheumatoid Synovial Cells by directly inhibiting caspase-3 activation. Thus, we propose that NO interferes with Cell death signal transduction and may contribute to rheumatoid Synovial Cell proliferation by inhibiting induction of apoptosis.
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Regulation of Rheumatoid Synovial Cell Growth by Ceramide
Biochemical and biophysical research communications, 2000Co-Authors: Kiyoshi Migita, Satoshi Yamasaki, Hiroaki Ida, Takahiko Aoyagi, Masako Kita, Seiyo Honda, Yasuko Hirai, Takaaki Fukuda, Toshiaki Tsukada, Atsushi KawakamiAbstract:Overgrowth of rheumatoid synoviocytes, which results in joint destruction, is due to impaired balance between Cell proliferation and Cell death (apoptosis). Ceramide is an important lipid messenger involved in mediating a variety of Cell functions including apoptosis. We investigated the effects of ceramide on growth-promoting anti-apoptotic signals in rheumatoid Synovial Cells. Human Synovial Cells isolated from patients with rheumatoid arthritis (RA) were stimulated with platelet-derived growth factor (PDGF) in the presence or absence of C2-ceramide. The kinase activity of Akt, MEK, and ERK1/2 was analyzed in PDGF-stimulated Synovial Cells by Western blot analysis. Pretreatment with C2-ceramide completely inhibited PDGF-induced Cell cycle progression of rheumatoid Synovial Cells. PDGF stimulation induced phosphorylation and activation of Akt, MEK, and ERK1/2 in rheumatoid Synovial Cells. C2-ceramide inhibited the activation of Akt, MEK and ERK1/2 in PDGF-stimulated Synovial Cells. Our data demonstrated that inhibition of anti-apoptotic kinases, such as Akt and ERK1/2, may play an important role in ceramide-mediated apoptosis of rheumatoid Synovial Cells.
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Regulation of Synovial Cell apoptosis by proteasome inhibitor.
Arthritis and rheumatism, 1999Co-Authors: Atsushi Kawakami, Satoshi Yamasaki, Hiroaki Ida, Tomoki Nakashima, Hideaki Sakai, Ayumi Hida, Satoshi Urayama, Hideki Nakamura, Yasufumi Ichinose, Takahiko AoyagiAbstract:Objective. Recent studies have shown the importance of proteasome function in the regulation of apoptosis. This study examined whether inhibition of proteasome function mediates apoptosis of Synovial Cells, and whether cytokines modulate this process. Methods. Type B Synovial Cells (fibroblast-like Synovial Cells) were cultured with tumor necrosis factor a (TNFa) or transforming growth factor b1 (TGFb1), and further incubated in the presence of variable concentrations of Z-Leu-Leu-Leu-aldehyde (LLL-CHO), a proteasome inhibitor. During this process, apoptosis of Synovial Cells was determined by Hoechst 33258 dye staining and 51 Cr release assay. The involvement of caspase cascade was examined using enzyme activity assay and blocking experiments by peptide inhibitors. The expression of pro-caspases, Bcl-2‐related proteins, and X chromosome‐linked inhibitor of apoptosis (XIAP) in Synovial Cells was examined by Western blot analysis. Results. Apoptosis of cultured Synovial Cells was induced in a dose-dependent manner by LLL-CHO. Activation of caspase cascade through caspase-8 to caspase-3 was essential during this process. Pretreatment of Synovial Cells with TNFa significantly augmented both the activation of caspases and the proportion of apoptosis in Synovial Cells induced by LLL-CHO, whereas TGFb1 pretreatment markedly suppressed these phenomena. The ratio of the expression of Bcl-2 to Bax or Bcl-xL to Bax, and XIAP expression in Synovial Cells may not be directly associated with the susceptibility of Synovial Cells to apoptosis by LLL-CHO. Conclusion. Apoptosis of Synovial Cells was induced by inhibition of proteasome function through the activation of caspase cascade, and this process was clearly modulated by cytokines. These data provide new insight into the regulatory mechanisms controlling Synovial Cells in rheumatoid synovitis by proteasome inhibitors, and might be useful for the design of new therapeutic strategies in rheumatoid arthritis.
Satoshi Yamasaki - One of the best experts on this subject based on the ideXlab platform.
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synoviolin hrd1 an e3 ubiquitin ligase as a novel pathogenic factor for arthropathy
Genes & Development, 2003Co-Authors: Tetsuya Amano, Satoshi Yamasaki, Naoko Yagishita, Kaneyuki Tsuchimochi, Hiroshi Shin, Koichi Kawahara, Satoko Aratani, Hidetoshi Fujita, Lei Zhang, Rie IkedaAbstract:Rheumatoid arthritis (RA) is one of the most critical articular diseases with Synovial hyperplasia followed by impairment of quality of life. However, the mechanism(s) that regulates Synovial Cell outgrowth is not fully understood. To clarify its mechanism(s), we carried out immunoscreening by using antirheumatoid Synovial Cell antibody and identified and cloned “Synoviolin/Hrd1”, an E3 ubiquitin ligase. Synoviolin/Hrd1 was highly expressed in the rheumatoid synovium, and mice overexpressing this enzyme developed spontaneous arthropathy. Conversely, synoviolin/hrd1+/- mice were resistant to collagen-induced arthritis by enhanced apoptosis of Synovial Cells. We conclude that Synoviolin/Hrd1 is a novel causative factor for arthropathy by triggering Synovial Cell outgrowth through its antiapoptotic effects. Our findings provide a new pathogenetic model of RA and suggest that Synoviolin/Hrd1 could be targeted as a therapeutic strategy for RA.
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Nitric oxide protects cultured rheumatoid Synovial Cells from Fas-induced apoptosis by inhibiting caspase-3.
Immunology, 2001Co-Authors: Kiyoshi Migita, Satoshi Yamasaki, Hiroaki Ida, Takahiko Aoyagi, Masako Kita, Kazutaka Shibatomi, Atsushi Kawakami, Katsuni EguchiAbstract:Nitric oxide (NO) is elevated in the Synovial fluids and sera of patients with rheumatoid arthritis (RA) and is thought to be an important proinflammatory mediator in the rheumatoid synovium. To test the hypothesis that NO might modulate the apoptosis-inducing signal pathway, we investigated the effects of NO on rheumatoid Synovial-Cell apoptosis induced by Fas ligation with anti-Fas antibody. Pretreatment of Synovial Cells with the NO donor S-nitro-N-acetylpenicillamine (SNAP) prevented the Fas-mediated induction of apoptosis. The activation of caspase-3 was required to mediate Fas-induced Synovial Cell apoptosis. The NO donor SNAP inhibited Fas-induced caspase-3 activation in rheumatoid Synovial Cells. However, NO did not interrupt Fas-induced caspase-8 cleavage or subsequent cytochrome c release into the cytosol in rheumatoid Synovial Cells. These data indicate that NO prevents apoptosis in rheumatoid Synovial Cells by directly inhibiting caspase-3 activation. Thus, we propose that NO interferes with Cell death signal transduction and may contribute to rheumatoid Synovial Cell proliferation by inhibiting induction of apoptosis.
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Regulation of Rheumatoid Synovial Cell Growth by Ceramide
Biochemical and biophysical research communications, 2000Co-Authors: Kiyoshi Migita, Satoshi Yamasaki, Hiroaki Ida, Takahiko Aoyagi, Masako Kita, Seiyo Honda, Yasuko Hirai, Takaaki Fukuda, Toshiaki Tsukada, Atsushi KawakamiAbstract:Overgrowth of rheumatoid synoviocytes, which results in joint destruction, is due to impaired balance between Cell proliferation and Cell death (apoptosis). Ceramide is an important lipid messenger involved in mediating a variety of Cell functions including apoptosis. We investigated the effects of ceramide on growth-promoting anti-apoptotic signals in rheumatoid Synovial Cells. Human Synovial Cells isolated from patients with rheumatoid arthritis (RA) were stimulated with platelet-derived growth factor (PDGF) in the presence or absence of C2-ceramide. The kinase activity of Akt, MEK, and ERK1/2 was analyzed in PDGF-stimulated Synovial Cells by Western blot analysis. Pretreatment with C2-ceramide completely inhibited PDGF-induced Cell cycle progression of rheumatoid Synovial Cells. PDGF stimulation induced phosphorylation and activation of Akt, MEK, and ERK1/2 in rheumatoid Synovial Cells. C2-ceramide inhibited the activation of Akt, MEK and ERK1/2 in PDGF-stimulated Synovial Cells. Our data demonstrated that inhibition of anti-apoptotic kinases, such as Akt and ERK1/2, may play an important role in ceramide-mediated apoptosis of rheumatoid Synovial Cells.
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Regulation of Synovial Cell apoptosis by proteasome inhibitor.
Arthritis and rheumatism, 1999Co-Authors: Atsushi Kawakami, Satoshi Yamasaki, Hiroaki Ida, Tomoki Nakashima, Hideaki Sakai, Ayumi Hida, Satoshi Urayama, Hideki Nakamura, Yasufumi Ichinose, Takahiko AoyagiAbstract:Objective. Recent studies have shown the importance of proteasome function in the regulation of apoptosis. This study examined whether inhibition of proteasome function mediates apoptosis of Synovial Cells, and whether cytokines modulate this process. Methods. Type B Synovial Cells (fibroblast-like Synovial Cells) were cultured with tumor necrosis factor a (TNFa) or transforming growth factor b1 (TGFb1), and further incubated in the presence of variable concentrations of Z-Leu-Leu-Leu-aldehyde (LLL-CHO), a proteasome inhibitor. During this process, apoptosis of Synovial Cells was determined by Hoechst 33258 dye staining and 51 Cr release assay. The involvement of caspase cascade was examined using enzyme activity assay and blocking experiments by peptide inhibitors. The expression of pro-caspases, Bcl-2‐related proteins, and X chromosome‐linked inhibitor of apoptosis (XIAP) in Synovial Cells was examined by Western blot analysis. Results. Apoptosis of cultured Synovial Cells was induced in a dose-dependent manner by LLL-CHO. Activation of caspase cascade through caspase-8 to caspase-3 was essential during this process. Pretreatment of Synovial Cells with TNFa significantly augmented both the activation of caspases and the proportion of apoptosis in Synovial Cells induced by LLL-CHO, whereas TGFb1 pretreatment markedly suppressed these phenomena. The ratio of the expression of Bcl-2 to Bax or Bcl-xL to Bax, and XIAP expression in Synovial Cells may not be directly associated with the susceptibility of Synovial Cells to apoptosis by LLL-CHO. Conclusion. Apoptosis of Synovial Cells was induced by inhibition of proteasome function through the activation of caspase cascade, and this process was clearly modulated by cytokines. These data provide new insight into the regulatory mechanisms controlling Synovial Cells in rheumatoid synovitis by proteasome inhibitors, and might be useful for the design of new therapeutic strategies in rheumatoid arthritis.
W. Widenmayer - One of the best experts on this subject based on the ideXlab platform.
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Pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome: differential diagnosis of septic arthritis by regular detection of exceedingly high Synovial Cell counts
Infection, 2017Co-Authors: W. Löffler, P. Lohse, T. Weihmayr, W. WidenmayerAbstract:Pyogenic arthritis, pyoderma gangrenosum and acne syndrome was diagnosed in a 42-year-old patient, after an unusual persistency of high Synovial Cell counts had been noticed. Clinical peculiarities and problems with diagnosing septic versus non-septic arthritis are discussed.
