Regulation of synovial cell apoptosis by proteasome inhibitor

Kawakami, Atsushi; Nakashima, Tomoki; Sakai, Hideaki; Hida, Ayumi; Urayama, Satoshi; Yamasaki, Satoshi; Nakamura, Hideki; Ida, Hiroaki; Ichinose, Yasufumi; Aoyagi, Takahiko; Furuichi, Itaru; Nakashima, Munetoshi; Migita, Kiyoshi; Kawabe, Yojiro; Eguchi, Katsumi

doi:10.1002/1529-0131(199911)42:11<2440::aid-anr23>3.0.co;2-0

Cited by 40 publications

(28 citation statements)

References 26 publications

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“…The hyperplasia of invasive synovial cells has been proposed to be due to an imbalance between cell proliferation and apoptotic cell death (Eguchi, 2001). Therefore, the identification of agents that induce apoptosis in rheumatoid synovial cells may be a key step toward the successful treatment of rheumatoid arthritis (Hui et al, 1997;Kawakami et al, 1999). In this study, we demonstrated that some of the NSAIDs induce apoptosis in rheumatoid synovial cells.…”

Section: Discussionmentioning

confidence: 65%

Nonsteroidal Anti-Inflammatory Drugs Induce Apoptosis in Association with Activation of Peroxisome Proliferator-Activated Receptor γ in Rheumatoid Synovial Cells

Yamazaki¹,

Kusunoki²,

Matsuzaki³

et al. 2002

The Journal of Pharmacology and Experimental Therapeutics

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Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to induce apoptosis in a variety of cell lines. In this study, we examined the effect of NSAIDs on the growth and apoptosis of synovial cells from patients with rheumatoid arthritis and analyzed the activation of peroxisome proliferator-activated receptor ␥ (PPAR␥) as a possible mechanism of action of NSAIDs. Cell proliferation and viability were assessed from 5-bromo-2Ј-deoxyuridine incorporation and by 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1) assay, respectively. The apoptosis of synovial cells was identified by DNA fragmentation assay and terminal deoxynucleotidyl transferasemediated dUTP nick-end labeling assay. Indometacin, diclofenac, oxaprozin, and zaltoprofen reduced cell proliferation and induced apoptotic cell death in synovial cells, whereas ketoprofen and acetaminophen did not. N-[2-(cyclohexyloxyl)-4-nitrophenyl]-methanesulfonamide (NS-398), a selective cyclooxygenase-2 inhibitor, also inhibited cell proliferation, whereas it did not cause apoptosis. Rheumatoid synovial cells expressed PPAR␥ mRNA, and the PPAR␥ ligands 15-deoxy-⌬ 12,14 -prostaglandin J 2 and troglitazone reduced the proliferation and induced apoptosis in synovial cells. Luciferase reporter assay demonstrated that not only PPAR␥ ligands but also NSAIDs, which could induce apoptosis, increased the activation of PPAR␥ in synovial cells. Furthermore, the ability of NSAIDs and PPAR␥ ligands to stimulate the activation of PPAR␥ correlated with their ability to decrease cell viability(r ϭ 0.92, p Ͻ 0.01) and ability to induce DNA fragmentation (r ϭ 0.97, p Ͻ 0.001) in synovial cells. These results suggest that PPAR␥ is an attractive target for induction of apoptosis in rheumatoid synovial cells and that the activation of the PPAR␥ pathway is associated with the apoptotic action of NSAIDs.

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Section: Discussionmentioning

confidence: 65%

Nonsteroidal Anti-Inflammatory Drugs Induce Apoptosis in Association with Activation of Peroxisome Proliferator-Activated Receptor γ in Rheumatoid Synovial Cells

Yamazaki¹,

Kusunoki²,

Matsuzaki³

et al. 2002

The Journal of Pharmacology and Experimental Therapeutics

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“…Tax expression has been reported to be both proapoptotic (Chen et al, 1997a;Chlichlia et al, 1997) and anti-apoptotic Copeland et al, 1994;Tsukahara et al, 1999), even using identical experimental systems, such as JPX-9 cells (Chen et al, 1997a;Kawakami et al, 1999 TRAIL/Apo-2L and caspase-10, both apoptosis inducers in various biological settings (FernandesAlnemri et al, 1996;Wiley et al, 1995). Relevant to these results, we noted that a previous microarray study comparing the expression patterns of HTLV-1-immortalized T-cells to normal T-cells described the strong up-regulation of cIAP 1 (anti-apoptotic factor) and Nip3 (pro-apoptotic factor) mRNA (Harhaj et al, 1999).…”

Section: Apoptosis-related Genesmentioning

confidence: 99%

Genome-wide expression changes induced by HTLV-1 Tax: evidence for MLK-3 mixed lineage kinase involvement in Tax-mediated NF-κB activation

et al. 2001

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The Tax protein of human T-lymphotropic virus type 1 (HTLV-1), an oncoprotein that transactivates viral and cellular genes, plays a key role in HTLV-1 replication and pathogenesis. We used cDNA microarrays to examine Tax-mediated transcriptional changes in the human Jurkat T-cell lines JPX-9 and JPX-M which express Tax and Tax-mutant protein, respectively, under the control of an inducible promoter. Approximately 300 of the over 2000 genes examined were di erentially expressed in the presence of Tax. These genes were grouped according to their function and are discussed in the context of existing ®ndings in the literature. There was strong agreement between our results and genes previously reported as being Tax-responsive. Genes that were di erentially expressed in the presence of Tax included those related to apoptosis, the cell cycle and DNA repair, signaling factors, immune modulators, cytokines and growth factors, and adhesion molecules. Functionally, we provide evidence that one of these genes, the mixed-lineage kinase MLK-3, is involved in Tax-mediated NF-kB signaling. Our current results provide additional insights into Tax-mediated signaling. Oncogene (2001) 20, 4484 ± 4496.

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“…Tax HTLV-1 regulates the expression of several cellular genes, including genes encoding cytokines (interleukin-2 (IL-2)), cytokine receptors (a chain of IL-2 receptor), and proto-oncogenes (c-fos, c-jun, fra-1, c-myc) (Cross et al, 1987;Ballard et al, 1988;Fujii et al, 1988Fujii et al, , 1991Tsuchiya et al, 1993;Semmes et al, 1996). Tax HTLV-1 targets regulators of cell cycle progression and apoptosis such as cyclin D2, cyclin-dependent kinase (cdk) 4, cdk6, the INK4 family of cdk inhibitors, Bcl-x L , Bax, DNA polymerase b, p53, caspase-8, and caspase-3 (Jeang et al, 1990;Suzuki et al, 1996;Brauweiler et al, 1997;Neuveut et al, 1998;Schmitt et al, 1998;Kawakami et al, 1999;Santiago et al, 1999;Pise-Masison et al, 2000;Mori et al, 2001). Mechanistically, Tax HTLV-1 was found to act essentially through CREB/ATF and NFkB signaling pathways (Sun and Ballard, 1999).…”

Section: Introductionmentioning

confidence: 99%

Disruption of B-cell homeostatic control mediated by the BLV-Tax oncoprotein: association with the upregulation of Bcl-2 and signaling through NF-κB

Szynal

Cleuter

Beskorwayne³

et al. 2003

Oncogene

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Regulation of synovial cell apoptosis by proteasome inhibitor

Cited by 40 publications

References 26 publications

Nonsteroidal Anti-Inflammatory Drugs Induce Apoptosis in Association with Activation of Peroxisome Proliferator-Activated Receptor γ in Rheumatoid Synovial Cells

Nonsteroidal Anti-Inflammatory Drugs Induce Apoptosis in Association with Activation of Peroxisome Proliferator-Activated Receptor γ in Rheumatoid Synovial Cells

Genome-wide expression changes induced by HTLV-1 Tax: evidence for MLK-3 mixed lineage kinase involvement in Tax-mediated NF-κB activation

Disruption of B-cell homeostatic control mediated by the BLV-Tax oncoprotein: association with the upregulation of Bcl-2 and signaling through NF-κB

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