BH3-only proteins in rheumatoid arthritis: potential targets for therapeutic intervention.
Rheumatoid arthritis (RA) is a debilitating disease, resulting in the destruction of bone and cartilage, and in the permanent disfigurement of joints. Although the precise cause of RA is currently unresolved, it has become clear that the damaging effects are a result of the toxic milieu caused by an influx of inflammatory cells and the resulting heightened proinflammatory state within the joint. As the amount of literature suggesting that this preponderance of cells is a result of decreased local apoptosis in the joint continues to increase, in this review, we describe how Bcl-2 family pro-apoptotic BH3-only proteins, particularly Bim and Bid, could act to protect against the development of the disease. We also suggest a role for BH3-mimetic drugs as potential therapeutics in the treatment of RA.
Hutcheson
J
J
Rheumatic Diseases Division, Department of Internal Medicine, University of Texas - Southwestern Medical Center, Simmons Arthritis Research Center, Dallas, TX, USA.
Perlman
H
H
D000818:Animals; D018501:Antirheumatic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000819:agonists* / Q000502:physiology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D015551:Autoimmunity / Q000187:drug effects / Q000502:physiology; D051023:BH3 Interacting Domain Death Agonist Protein / Q000819:agonists* / Q000502:physiology; D000072224:Bcl-2-Like Protein 11; D016503:Drug Delivery Systems; D015195:Drug Design; D005786:Gene Expression Regulation; D006801:Humans; D007211:Indoles; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008565:Membrane Proteins / Q000819:agonists* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000819:agonists* / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000145:classification / Q000172:deficiency / Q000502:physiology*; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use; D013329:Structure-Activity Relationship; D016176:T-Lymphocyte Subsets / Q000276:immunology
D018501:Antirheumatic Agents; D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D007211:Indoles; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011758:Pyrroles; C520962:obatoclax