title: The role of apoptosis in rheumatoid arthritis.
abstract: 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-alpha 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.
authors.affiliation: Northwestern University Feinberg School of Medicine and the VA Medical Center, Chicago, Lakeside Division Department of Medicine, Division of Rheumatology, 303 East Chicago Avenue, Tarry 3-377, Chicago IL 60611, USA.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Liu
authors.forename: Richard M
authors.initials: RM
authors.lastname: Pope
mesh_terms: D017209:Apoptosis; D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology; D053222:Fas Ligand Protein; D019254:Genes, bcl-2 / Q000502:physiology; D016158:Genes, p53 / Q000502:physiology; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism / Q000502:physiology; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism / Q000502:physiology; D019014:fas Receptor / Q000378:metabolism / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D050796:STAT3 Transcription Factor; D015534:Trans-Activators; D019014:fas Receptor; C505661:FASLG protein, human; C494086:STAT3 protein, human; C494918:AKT1 protein, human