Expression of Fas-associated death domain-like interleukin-1beta-converting enzyme (FLICE) inhibitory protein (FLIP) in human articular chondrocytes: possible contribution to the resistance to Fas-mediated death of in vitro cultured human articular chondrocytes.
Although chondrocyte apoptosis has been noted in arthritic joints, the mechanism is not clear. To investigate whether Fas-mediated apoptosis has a role in this process, the presence of Fas mRNA and expression of cell surface Fas protein in monolayer-cultured human articular chondrocytes was analyzed. Fas mRNA was found in all chondrocyte samples analyzed; moreover, the majority of cells in chondrocyte populations expressed cell-surface Fas (12-90%, average 49%). Nevertheless, treatment with an agonistic anti-Fas antibody did not induce significant apoptosis in these chondrocytes in vitro. However, it was also found that chondrocytes express Fas-associated death domain-like interleukin-1beta-converting enzyme-inhibitory protein (FLIP), a molecule which blocks Fas-mediated apoptosis. Correspondingly, activation of caspase-8 was minimal in these cultured chondrocytes. In conclusion, although human articular chondrocytes do express cell-surface Fas, this receptor did not fully mediate death-inducing signals in vitro. This resistance to Fas may be partly due to the constitutive expression of FLIP.
Masuko-Hongo
K
K
Institute of Medical Science. St. Marianna University School of Medicine, Kawasaki-shi, Kanagawa, Japan. khongo@marianna-u.ac.jp
Sakata
M
M
Yuan
G H
GH
Onuma
H
H
Nakamura
H
H
Aoki
H
H
Kato
T
T
Nishioka
K
K
D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism*; D011506:Proteins / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
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