Apoptosis in rheumatoid arthritis synovium.

Abstract

RA synovial tissue (ST) was studied to determine if and where apoptosis occurs in situ. Genomic DNA was extracted from 5 RA and 1 osteoarthritis ST samples. Agarose gel electrophoresis demonstrated DNA ladders characteristic for apoptosis from each tissue. In situ end labeling (ISEL) was used to identify DNA strand breaks consistent with apoptosis in frozen sections. 12 RA and 4 osteoarthritis ST were studied by ISEL and all were positive, but only 2 of 4 normal tissues were positive. The primary location of apoptotic cells was the synovial lining. Some sublining cells were also positive, but lymphoid aggregate staining was conspicuously absent. Immunohistochemistry and ISEL were combined and showed that the lining cells with DNA strand breaks were mainly macrophages, although some fibroblastlike cells were also labeled. Sublining cells with fragmented DNA included macrophages and fibroblasts, but T cells in lymphoid aggregates, which expressed large amounts of bcl-2, were spared. DNA strand breaks in cultured fibroblastlike synoviocytes was assessed using ISEL. Apoptosis could be induced by actinomycin D, anti-fas antibody, IL-1, and TNF-a but not by IFN-y. Fas expression was also detected on fibroblast-like synoviocytes using flow cytometry. Therefore, DNA strand breaks occur in synovium of patients with arthritis. Cytokines regulate this process, and the cytokine profile in RA (high IL-1/TNF; low IFN-y) along with local oxidant injury might favor induction of apoptosis. (J. Clin. Invest. 1995.96:1631-1638

Constitutive expression of BCL‐XL in the T lineage attenuates collagen‐induced arthritis in Bcl‐XL transgenic mice

“…Resistance to apoptosis in peripheral blood T cells and synovial T cells has been suggested to play an important role in the pathogenesis of RA (3,4). Indeed, induced apoptosis of activated arthritogenic T lymphocytes has been considered as a potential therapeutic strategy (19).…”

“…Resistance to cell death has been implicated in autoimmune diseases such as diabetes mellitus (1) and experimental autoimmune encephalomyelitis (EAE) (2). In rheumatoid arthritis (RA), apoptosis was detected in macrophages and fibroblasts, but not in T lymphocyte aggregates, in patient synovium (3,4). In addition, RA patients have a subset of CD4ϩ,CD28Ϫ T cells in the peripheral blood that frequently undergoes clonal expansion and is resistant to apoptosis (5).…”

Mycoplasma fermentans inhibits tumor necrosis factor α-induced apoptosis in the human myelomonocytic U937 cell line

“…1 Mycoplasma fermentans (M. fermentans), a human pathogen, was shown to induce polyclonal activation of the immune cells, cytokine production, increased major histocompatibility complex (MHC) class II expression, increased cytotoxicity of T cells and expression of oncogenes. [2][3][4][5][6] In the last decade, there have been increasing numbers of publications implicating M. fermentans in the development of rheumatoid arthritis (RA), [7][8][9] a disease characterized by impaired apoptosis. 8,[10][11][12] Apoptosis is induced in two different pathways: the intrinsic and extrinsic pathways.…”

Signal transduction pathways and apoptosis in bacteria infected chondrocytes

“…Bacterial toxins and cytokines are known inducers of apoptosis [5,16,27]. However, previous studies about apoptosis in articular cartilage have been focused on synovial apoptosis in rheumatoid arthritis [4,9,18], in endochondral ossification, and in chondrogenesis [1,10-121. The role of *Corresponding author.…”