OBJECTIVE: To evaluate the Fas-dependent signaling pathway, we examined the involvement of protein tyrosine phosphorylation and the DNA binding activity of AP-1 in rheumatoid arthritis (RA) cultured synovial cells. METHODS: The number of dead cells was counted after treatment with anti-Fas antibody in the presence of protein tyrosine kinase or phosphatase inhibitor. Protein tyrosine phosphorylation in synoviocytes after Fas ligation was examined by immunoblot and immunoprecipitation analyses. The DNA binding activity of AP-1 was examined by electrophoretic mobility shift assay. RESULTS: Treatment with the protein tyrosine phosphatase inhibitor, orthovanadate, significantly enhanced the apoptosis of RA synoviocytes after Fas ligation. Ligation of the Fas molecule 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 signaling pathway is activated during the process of Fas-mediated apoptosis of RA synovial cells.
OBJECTIVE: To evaluate the Fas-dependent signaling pathway, we examined the involvement of protein tyrosine phosphorylation and the DNA binding activity of AP-1 in rheumatoid arthritis (RA) cultured synovial cells. METHODS: The number of dead cells was counted after treatment with anti-Fas antibody in the presence of protein tyrosine kinase or phosphatase inhibitor. Protein tyrosine phosphorylation in synoviocytes after Fas ligation was examined by immunoblot and immunoprecipitation analyses. The DNA binding activity of AP-1 was examined by electrophoretic mobility shift assay. RESULTS: Treatment with the protein tyrosine phosphatase inhibitor, orthovanadate, significantly enhanced the apoptosis of RA synoviocytes after Fas ligation. Ligation of the Fas molecule 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 signaling pathway is activated during the process of Fas-mediated apoptosis of RA synovial cells.
Authors: Noreen Pundt; Marvin A Peters; Christina Wunrau; Simon Strietholt; Carsten Fehrmann; Katja Neugebauer; Christine Seyfert; Frans van Valen; Thomas Pap; Ingmar Meinecke Journal: Arthritis Res Ther Date: 2009-02-05 Impact factor: 5.156
Authors: Chelsea L Edwards; Marcela Montes de Oca; Fabian de Labastida Rivera; Rajiv Kumar; Susanna S Ng; Yulin Wang; Fiona H Amante; Kohei Kometani; Tomohiro Kurosaki; Tom Sidwell; Axel Kallies; Christian R Engwerda Journal: Front Immunol Date: 2018-11-06 Impact factor: 7.561