Review: Apoptosis in rheumatoid arthritis: A novel pathway in the regulation of synovial tissue

Nishioka, Kusuki; Hasunuma, Tomoko; Kato, Tomohiro; Sumida, Takayuki; Kobata, Tetsuji

doi:10.1002/1529-0131(199801)41:1<1::aid-art1>3.0.co;2-v

Cited by 82 publications

(16 citation statements)

References 78 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This may result in the persistence of T cells with reduced capacity for cytokine production, despite maintenance of their B cell stimulatory function in RA. 109,113,[119][120][121] This functional state may explain the lack of clinical benefit observed with immunotherapy directed solely at T cells in the chronic phase of RA.…”

Section: Do Synovial DC Perpetuate Ra By the Efficient Presentation Omentioning

confidence: 99%

Dendritic cells: The driving force behind autoimmunity in rheumatoid arthritis?

Pettit

Thomas

1999

Immunol Cell Biol

View full text Add to dashboard Cite

IntroductionDendritic cells (DC) are the professional APC of the immune system. As such, they are the only APC capable of priming the immune response and the most efficient stimulators of memory responses. In addition, their role in the generation of central tolerance is well known and recent evidence implicates DC in various forms of peripheral tolerance. [1][2][3][4][5][6][7] The DC function as effective APC because of their efficient antigen capture and processing functions, migratory and cell surface remodelling ability and potent T cell stimulatory capacity. 4,[8][9][10][11][12][13] In addition, DC are likely to play a role in the regulation of B cell growth, differentiation and immunoglobulin class switching that is separate to that of follicular DC. 4,[14][15][16][17] Two DC subsets, the classical myeloid-related DC and a novel lymphoid-related DC, have been identified and recent evidence suggests that each of these subsets may have different roles in the generation of peripheral tolerance or immunity and in the type of T cell response. [18][19][20][21][22] It has been proposed that DC are the critical decision-making cells in the immune system. Thus, DC respond to local factors that facilitate decisions about the nature of the T cell response. The various signals that influence the DC are not yet fully elucidated, but these signals are likely to depend on the type and dose of antigen, the micro-environment of the DC-antigen encounter, the number, subset and phenotype of the DC involved and the micro-environment of the secondary lymphoid organs where the antigen is presented. 4,8,9,23,24 Functional differentiation of DC Myeloid-related DC (to be referred to as DC for the remainder of this paper) are found in most tissues, solid organs and blood as immature sentinel cells that are continually sampling the environment for self and non-self antigens. The DC can capture and present antigen at picomolar and nanomolar concentrations. 25 These immature DC also process antigen efficiently and produce large amounts of MHC class II molecules that are localized to specialised MHC class II-rich late-endosomal compartments (MIIC). The MIIC contain all the necessary machinery required to edit and load peptides into MHC class II molecules and efficiently transport the peptide-loaded molecules to the cell surface for interaction with T cells. 4,13,[26][27][28][29][30][31][32] The combination of antigen and inflammatory signals, including granulocyte-macrophage colony stimulating factor (GM-CSF), LPS, TNF-α and IL-1, stimulates differentiation and migration of peripheral DC via the afferent lymphatics to draining lymph node (LN). During this differentiation process, DC down-regulate their antigen capture and processing ability, while up-regulating the expression of molecules required for efficient antigen presentation, including peptide-loaded MHC class I and II, costimulatory molecules CD80 and CD86, CC-chemokine receptor (CCR)7 and adhesion molecules that are involved in the direct interaction of DC with T cells. In the...

show abstract

Section: Do Synovial DC Perpetuate Ra By the Efficient Presentation Omentioning

confidence: 99%

Dendritic cells: The driving force behind autoimmunity in rheumatoid arthritis?

Pettit

Thomas

1999

Immunol Cell Biol

View full text Add to dashboard Cite

show abstract

“…However, rheumatoid synovial cells are sensitive to Fas‐mediated apoptosis. Several studies have indicated that spontaneous growth arrest and remission occur in RA synovial cells, which express functional Fas (CD95) and show Fas‐mediated apoptosis both in vitro and in vivo (3–6). These paradoxical features of RA synovium associated with an imbalance between cell proliferation and cell death appear to be highly relevant to the pathologic processes of RA synovitis.…”

mentioning

confidence: 99%

β1 integrin–mediated signaling induces intercellular adhesion molecule 1 and Fas on rheumatoid synovial cells and Fas‐mediated apoptosis

Nakayamada

Saito

Fujii

et al. 2003

Arthritis & Rheumatism

View full text Add to dashboard Cite

Objective. Rheumatoid arthritis (RA) synovial cells interact with inflammatory cells, as well as extracellular matrices, through integrins. However, the relevance of ␤1 integrin to inflammatory processes in RA remains unclear. We examined the role of ␤1 integrinmediated signaling in RA.Methods. Expression of cell-surface molecules was assessed by FACScan. Engagement of ␤1 integrins was performed by crosslinking using a specific monoclonal antibody (mAb) and ligand matrices such as fibronectin or collagen. To determine the involvement of tyrosine kinases in ␤1 integrin-mediated signaling, the cells were pretreated with various inhibitors of intracytoplasmic signaling or were transfected with a wildtype focal adhesion kinase (

show abstract

“…RA is characterized by extensive inflammation and proliferation of the synovium in various joints. Nishioka et al (12) have suggested that stimulation of proliferation by tumor necrosis factor α and induction of apoptosis by Fas ligand play an important role in regulating the growth of rheumatoid synovial tissue. Although NSAIDs (even selective COX‐2 inhibitors) are generally considered to have little disease‐modifying effect in RA, some NSAIDs have been reported to suppress the proliferation of RASFs (10) and cancer cells (13, 14) by induction of apoptosis.…”

mentioning

confidence: 99%

Induction of apoptosis in rheumatoid synovial fibroblasts by celecoxib, but not by other selective cyclooxygenase 2 inhibitors

Kusunoki¹,

Yamazaki²,

Kawai³

2002

Arthritis & Rheumatism

View full text Add to dashboard Cite

Objective. Selective cyclooxygenase 2 (COX-2) inhibitors are now being used as antiinflammatory agents that cause fewer gastrointestinal complications, compared with other antiinflammatory drugs, in patients with rheumatoid arthritis (RA). This study was undertaken to investigate whether selective COX-2 inhibitors could induce apoptosis of RA synovial fibroblasts (RASFs).Methods. RASFs were exposed to selective COX-2 inhibitors, i.e., celecoxib, etodolac, meloxicam, nimesulide, N-[2-(cyclohexyloxyl)-4-nitrophenyl]-methanesulfonamide, and rofecoxib, under various conditions. Cell proliferation and cell viability were assessed by incorporation of 5-bromo-2 -deoxyuridine and by the 2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium monosodium salt assay, respectively. Apoptosis was detected by identifying DNA fragmentation. Activation of peroxisome proliferatoractivated receptor ␥ (PPAR␥) was measured by the luciferase reporter gene assay with a PPAR response element-driven luciferase reporter plasmid and a PPAR␥ expression plasmid.Results. Celecoxib strongly inhibited the proliferation of RASFs, whereas other selective COX-2 inhibitors had little or no effect. In addition, celecoxib reduced the viability of RASFs by induction of apoptosis, in a concentration-dependent manner. This action was abolished by addition of caspase inhibitors. Interleukin-1␤ had a weak enhancing effect on celecoxib-induced apoptosis in RASFs. In contrast, other selective COX-2 inhibitors at concentrations up to 100 M did not induce apoptosis of RASFs. Indomethacin, a nonselective COX inhibitor, activated PPAR␥ transcription, while celecoxib did not.Conclusion. Celecoxib suppressed the proliferation of RASFs by COX-2-independent and PPAR␥-independent induction of apoptosis. Although the mechanism involved remains unclear, celecoxib may have not only antiinflammatory activity, but also a diseasemodifying effect on rheumatoid synovial proliferation.

show abstract

Review: Apoptosis in rheumatoid arthritis: A novel pathway in the regulation of synovial tissue

Cited by 82 publications

References 78 publications

Dendritic cells: The driving force behind autoimmunity in rheumatoid arthritis?

Dendritic cells: The driving force behind autoimmunity in rheumatoid arthritis?

β1 integrin–mediated signaling induces intercellular adhesion molecule 1 and Fas on rheumatoid synovial cells and Fas‐mediated apoptosis

Induction of apoptosis in rheumatoid synovial fibroblasts by celecoxib, but not by other selective cyclooxygenase 2 inhibitors

Contact Info

Product

Resources

About