Bee venom induces apoptosis through caspase-3 activation in synovial fibroblasts of patients with rheumatoid arthritis.
Bee venom (BV) has been used traditionally for the control of pain and inflammation in various chronic inflammatory diseases, including rheumatoid arthritis (RA) in Oriental medicine. However, it is still unclear how BV exerts its beneficial effects on the clinical course of RA patients. To investigate the effect of BV on the treatment of rheumatoid synovitis, we examined the inhibition of cell growth and induction of apoptosis in human rheumatoid synovial fibroblasts. Rheumatoid synovial fibroblasts were surgically obtained from patients with RA. Cell proliferation and viability were assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The apoptosis of synovial cells treated with 10 microg/ml BV for 24 h was identified by 4,6-diamidino-2-phenylindole (DAPI) staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assay, DNA fragmentation assay, RT-PCR, and Western blot analysis. It was demonstrated that rheumatoid synovial cells treated with 10 microg/ml BV for 24 h exhibited apoptotic features and fragmentation of DNA. In addition, BV induces apoptosis in rheumatoid synovial cells through a decrease in BCL2 expression and an increase in BAX and caspase-3 (CASP3) expression. It is suggested that BV inhibits the proliferation of rheumatoid synovial cells through induction of apoptosis by CASP3 activation.
Hong
Seung-Jae
SJ
Department of Internal Medicine, College of Medicine, Pochon CHA University, 351 Yatap-dong, Bundang-gu, Sungnam-si, Kyonggi-do 463-712, South Korea.
Rim
Gyu Sung
GS
Yang
Hyung In
HI
Yin
Chang Shik
CS
Koh
Hyeong Gyun
HG
Jang
Mi-Hyeon
MH
Kim
Chang-Ju
CJ
Choe
Bong-Keun
BK
Chung
Joo-Ho
JH
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D001172:Arthritis, Rheumatoid / Q000201:enzymology / Q000503:physiopathology*; D001514:Bee Venoms / Q000494:pharmacology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004789:Enzyme Activation; D005347:Fibroblasts / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051028:bcl-2-Associated X Protein
D048868:Adaptor Proteins, Signal Transducing; C494826:BAX protein, human; C486655:BMF protein, human; D001514:Bee Venoms; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases