TY - JOUR
T1 - The role of apoptosis in rheumatoid arthritis
AU - Liu, Hongtao
AU - Pope, Richard M.
N1 - Funding Information:
Richard M Pope’s work was supported by awards from the National Institute of Health (N01-AR62221 and 1R01 AR049217), and The Veterans Administration Research Service (Merit Review) from the National and the Greater Chicagoland Chapters of The Arthritis Foundation. We thank Yingyu Ma for the preparation of the figure in the text.
PY - 2003/6
Y1 - 2003/6
N2 - Rheumatoid arthritis (RA) is a chronic inflammatory disease, which results in inflammation of the synovial lining and destruction of the adjacent bone and cartilage. Synovial macrophages, fibroblasts and lymphocytes are critical to the pathogenesis of this disease, in which apoptosis may play divergent roles. In joints of patients with active RA, few apoptotic cells are detected, and experimental data suggest that enhanced apoptosis within the joint might be therapeutically beneficial. Signaling pathways, such as the nuclear factor kappa-B, phosphatidylinositol 3-kinase/Akt-1 and signal transducer and activator of transcription-3 pathways, are highly activated in the RA joint. Activation of these pathways contributes not only to the expression of genes that cause inflammation and destruction but also to the expression of a variety of anti-apoptotic molecules, including FLICE inhibitory protein, Bcl-2, and Mcl-1, which protect against apoptosis that may be initiated through death receptor- or mitochondria-dependent pathways. The induction of apoptosis of macrophages, synovial fibroblasts or lymphocytes, either through suppression of signaling pathways or inhibition of the expression of anti-apoptotic molecules, could be therapeutically beneficial in RA. While tumour necrosis factor-α contributes to inflammation, destruction and protection against apoptosis in the RA joint (together with FasL), it also promotes apoptosis of bone marrow progenitor cells that contribute to anemia of chronic disease, which is very common in acute RA.
AB - Rheumatoid arthritis (RA) is a chronic inflammatory disease, which results in inflammation of the synovial lining and destruction of the adjacent bone and cartilage. Synovial macrophages, fibroblasts and lymphocytes are critical to the pathogenesis of this disease, in which apoptosis may play divergent roles. In joints of patients with active RA, few apoptotic cells are detected, and experimental data suggest that enhanced apoptosis within the joint might be therapeutically beneficial. Signaling pathways, such as the nuclear factor kappa-B, phosphatidylinositol 3-kinase/Akt-1 and signal transducer and activator of transcription-3 pathways, are highly activated in the RA joint. Activation of these pathways contributes not only to the expression of genes that cause inflammation and destruction but also to the expression of a variety of anti-apoptotic molecules, including FLICE inhibitory protein, Bcl-2, and Mcl-1, which protect against apoptosis that may be initiated through death receptor- or mitochondria-dependent pathways. The induction of apoptosis of macrophages, synovial fibroblasts or lymphocytes, either through suppression of signaling pathways or inhibition of the expression of anti-apoptotic molecules, could be therapeutically beneficial in RA. While tumour necrosis factor-α contributes to inflammation, destruction and protection against apoptosis in the RA joint (together with FasL), it also promotes apoptosis of bone marrow progenitor cells that contribute to anemia of chronic disease, which is very common in acute RA.
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U2 - 10.1016/S1471-4892(03)00037-7
DO - 10.1016/S1471-4892(03)00037-7
M3 - Review article
C2 - 12810199
AN - SCOPUS:0037840263
VL - 3
SP - 317
EP - 322
JO - Current Opinion in Pharmacology
JF - Current Opinion in Pharmacology
SN - 1471-4892
IS - 3
ER -