SELECTIVE ACTIVATION OF THE JNK AP-1 PATHWAY IN FAS-MEDIATED APOPTOSIS OF RHEUMATOID-ARTHRITIS SYNOVIOCYTES/

Objective. To evaluate the Fas-dependent signaling pathway, we examine d the involvement of protein tyrosine phosphorylation and the DNA bind ing activity of AP-1 in rheumatoid arthritis (RA) cultured synovial ce lls. Methods. The number of dead cells was counted after treatment wit h anti-Fas antibody in the presence of protein tyrosine kinase or phos phatase inhibitor. Protein tyrosine phosphorylation in synoviocytes af ter Pas ligation was examined by immunoblot and immunoprecipitation an alyses. The DNA binding activity of AP-1 was examined by electrophoret ic mobility shift assay. Results. Treatment with the protein tyrosine phosphatase inhibitor, orthovanadate, significantly enhanced the apopt osis of RA synoviocytes after Fas ligation. Ligation of the Pas molecu le on RA synoviocytes induced a rapid tyrosine phosphorylation of JNK (c-Jun amino-terminal kinase) and formation of the AP-1 transcription factor. Conclusion. Our results strongly suggest that the JNK/AP-1 sig naling pathway is activated during the process of Fas-mediated apoptos is of RA synovial cells.