Apoptosis in rheumatoid arthritis.
Apoptosis is a key mechanism that regulates tissue composition and homeostasis. Alterations in the apoptosis of synovial cells have been described in residential synoviocytes as well as inflammatory cells and associated with the pathogenesis of rheumatoid arthritis. These changes constitute hallmarks of synovial cell activation and contribute to both chronic inflammation and hyperplasia. Rheumatoid arthritis synovial fibroblasts are affected most prominently, and their resistance to apoptosis has been linked closely to the progressive destruction of articular cartilage. Although a detailed understanding of mechanisms that prevent synovial fibroblasts from programmed cell death is lacking, several antiapoptotic molecules have been identified. Among them, downstream modulators of Fas-signaling, such as sentrin-1/small ubiquitin-like modifier (SUMO)-1 and Fas-associated death domain-like interleukin (IL)-1beta-converting enzyme-inhibitory protein (FLIP), as well as transcriptional regulators such as NFkappaB, Stat3, and p53, have been suggested to regulate apoptosis most prominently. Current efforts are aimed at elucidating the specific role of these molecules in regulating the apoptosis of rheumatoid fibroblasts and at identifying molecular targets to interfere with altered apoptosis.
Baier
Anja
A
Division of Experimental Rheumatology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
Meineckel
Ingmar
I
Gay
Steffen
S
Pap
Thomas
T
D018501:Antirheumatic Agents / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000503:physiopathology*; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002352:Carrier Proteins; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D011322:Primary Prevention / Q000379:methods; D011379:Prognosis; D011506:Proteins; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D013583:Synovial Membrane / Q000166:cytology / Q000502:physiology
D018501:Antirheumatic Agents; D051017:Apoptosis Regulatory Proteins; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D002352:Carrier Proteins; C421307:FAIM protein, human; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins