Importance of NF-κB in rheumatoid synovial tissues: in situ NF-κB expression and in vitro study using cultured synovial cells

Yamasaki, Satoshi; Kawakami, Atsushi; Nakashima, Tomoki; Nakamura, Hideki; Kamachi, Makoto; Honda, Seiyo; Hirai, Yasuko; Hida, Ayumi; Ida, Hiroaki; Migita, Kiyoshi; Kawabe, Yojiro; Koji, Takehiko; Furuichi, Itaru; Aoyagi, Takahiko; Eguchi, Katsumi

doi:10.1136/ard.60.7.678

Cited by 49 publications

(29 citation statements)

References 33 publications

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“…Cell stimulation induces degradation of I B, resulting in nuclear translocation of the Rel/NF-B subunits and activation of transcription. Activated Rel/NF-B subunits are abundantly expressed in RA synovial tissue and in experimental models of arthritis (5)(6)(7)(8)(9). In studies involving experimental arthritis, there is evidence to suggest that the Rel/NF-B subunits play distinct roles in the pathogenesis of inflammatory arthritis (10).…”

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confidence: 99%

Increased synovial tissue NF‐κB1 expression at sites adjacent to the cartilage–pannus junction in rheumatoid arthritis

Benito

Murphy

et al. 2004

Arthritis & Rheumatism

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Objective. To compare the expression of the Rel/ NF-B subunits, NF-B1 (p50) and RelA (p65), in paired synovial tissue samples selected from sites adjacent to and remote from the cartilage-pannus junction (CPJ) in patients with inflammatory arthritis.Methods. Synovial tissue was selected at arthroscopy from sites adjacent to the CPJ and from the suprapatellar pouch of patients who were referred to an early arthritis clinic. Tissue samples from patients with osteoarthritis (OA) undergoing knee arthroplasty were also studied. Rel/NF-B subunit activation and expression were measured by electrophoretic mobility shift assay and supershift analyses and by immunohistochemistry.Results. Tissue samples were obtained from 10 patients with rheumatoid arthritis (RA), 7 with a seronegative arthropathy (SnA), and 6 with OA. Rel/NF-B was abundantly expressed in all samples. In both RA and SnA synovial tissue, the absolute number of NF-B1؉ cells at the CPJ was significantly higher than at non-CPJ sites (P ‫؍‬ 0.006 and P ‫؍‬ 0.02, respectively). The proportion of cells expressing NF-B1 was also significantly higher at the CPJ compared with non-CPJ sites (P ‫؍‬ 0.003 in RA, P ‫؍‬ 0.009 in SnA). The numbers of RelA؉ cells were consistently lower throughout. In RA synovial tissue, but not in SnA synovial tissue, both the absolute number and the proportion of RelA؉ cells were significantly higher at the CPJ than at non-CPJ sites (P ‫؍‬ 0.003 and P ‫؍‬ 0.01, respectively). In OA synovial tissue, the numbers of cells expressing NF-B1 and RelA were similar to those observed at the non-CPJ sites in all inflammatory tissues studied.Conclusion. In this study of early inflammatory arthritis, expression of NF-B1 in synovial tissue was highest at sites most likely to be associated with joint erosion. These observations are consistent with a critical role of NF-B1 in joint destruction, and support the rationale for specific therapeutic inhibition of NF-B in RA.

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confidence: 99%

Increased synovial tissue NF‐κB1 expression at sites adjacent to the cartilage–pannus junction in rheumatoid arthritis

Benito

Murphy

et al. 2004

Arthritis & Rheumatism

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“…Bcl-2 is highly expressed on synovial fibroblasts in the synovial lining and the sublining region from RA (54). Increased NF-kB binding activity in synovial tissue extracts by electrophoretic mobility shift assays and enhanced nuclear localization in the synovial lining have been demonstrated in RA compared with osteoarthritis (OA) (55)(56)(57). Collectively, these data suggest that Bcl-2 as well as NF-kB may be regulated by the inflammatory cytokine milieu.…”

Section: Apoptosis In Rheumatoid Arthritismentioning

confidence: 86%

“…Stimulation of TGF-p becomes markedly resistant to Fas-mediated and proteasome inhibitor-mediated apoptosis (52,58 2 (60). TNF-oc and IL-lp increase nuclear NF-kB activity (57). TNF-a may induce a death signal through a TNFR1-associated death domain (TRADD)or stimulate cell activation through the NFkB pathway, and the coincident inhibition of apoptosis (61,62).…”

Section: Apoptosis In Rheumatoid Arthritismentioning

confidence: 99%

“…TNF-a may induce a death signal through a TNFR1-associated death domain (TRADD)or stimulate cell activation through the NFkB pathway, and the coincident inhibition of apoptosis (61,62). Whereas the activation of NF-kBblocks cell killing, its inhibition enhances the cytotoxicity of TNF-aand promotes apoptosis in synovial cells (57,58).…”

Section: Apoptosis In Rheumatoid Arthritismentioning

confidence: 99%

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Apoptosis in Autoimmune Diseases.

Eguchi

2001

Intern. Med.

149

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Over the past decade, our understanding of apoptosis, or programmed cell death, has increased greatly, with the identification of someof the major componentsof the apoptotic program and the processes regulating their activation. Although apoptosis is an intrinsic process present in all cells, it can be regulated by extrinsic factors, including growth factors, cell surface receptors, cellular stress and hormones. Apoptotis plays an important role in autoimmunediseases. Normal thyrocytes could induce apoptosis of infiltrating activated T cells and protect against attack by such cells, i.e., the normal thyroid tissues act as an immune privileged site. In Hashimoto's thyroiditis (HT), Fasmediated apoptosis of thyrocytes in a section of tissues is due to at least two separate mechanisms, the first by infiltrating activated T cells, and the other by FasL-possitive thyrocytes in a suicidal or fratricidal fashion. A common feature of autoimmunediseases such as systemic lupus erythematosus (SLE) is the breakdown of tolerance of self antigens, a consequence of which is the production of autoantibodies reactive with multiple self proteins. Evidence is accumulating that modifications of autoantigens during apoptosis lead to the development of autoantibodies by bypassing the normal mechanisms of tolerance. Tissue homeostasis is maintained through a balance between cell proliferation and apoptotic cell death. Rheumatoid arthritis (RA) is characterized by pronounced hyperplasia of the synovial tissue, cell infiltration and periarticular osteoporosis. Enhanced Bcl-2 expression and NF-kBnuclear translocation of synovial cells are induced by inflammatory cytokines and/ or growth factors. These synovial cells become resistant toward apoptosis triggered by various stimuli. The infiltrated cells which are defect in activation-induced cell death can cause autoimmunity by allowing the survival of autoreactive T and B cells. These data suggest that apoptosis might be implicated with the pathogenesis of autoimmunity, whereas the mechanismsmight be distinct in each autoimmunedisease. (Internal Medicine 40: 275-284, 2001)

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“…The streptavidin-biotin method (Histofine Staining Kit; Nichirei Co., Tokyo, Japan) was used for immunohistochemical detection as described previously. 15 Briefly, endogenous peroxidase was inactivated by immersing the section in 3% hydrogen peroxide solution.…”

Section: Methodsmentioning

confidence: 99%

Antiangiogenic Gene Therapy for Hepatocellular Carcinoma Using Angiostatin Gene

Ishikawa

2003

Hepatology

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Importance of NF-κB in rheumatoid synovial tissues: in situ NF-κB expression and in vitro study using cultured synovial cells

Cited by 49 publications

References 33 publications

Increased synovial tissue NF‐κB1 expression at sites adjacent to the cartilage–pannus junction in rheumatoid arthritis

Increased synovial tissue NF‐κB1 expression at sites adjacent to the cartilage–pannus junction in rheumatoid arthritis

Apoptosis in Autoimmune Diseases.

Antiangiogenic Gene Therapy for Hepatocellular Carcinoma Using Angiostatin Gene

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