title: Bee venom induces apoptosis through caspase-3 activation in synovial fibroblasts of patients with rheumatoid arthritis.
abstract: 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.
authors.affiliation: Department of Internal Medicine, College of Medicine, Pochon CHA University, 351 Yatap-dong, Bundang-gu, Sungnam-si, Kyonggi-do 463-712, South Korea.
authors.forename: Seung-Jae
authors.initials: SJ
authors.lastname: Hong
authors.forename: Gyu Sung
authors.initials: GS
authors.lastname: Rim
authors.forename: Hyung In
authors.initials: HI
authors.lastname: Yang
authors.forename: Chang Shik
authors.initials: CS
authors.lastname: Yin
authors.forename: Hyeong Gyun
authors.initials: HG
authors.lastname: Koh
authors.forename: Mi-Hyeon
authors.initials: MH
authors.lastname: Jang
authors.forename: Chang-Ju
authors.initials: CJ
authors.lastname: Kim
authors.forename: Bong-Keun
authors.initials: BK
authors.lastname: Choe
authors.forename: Joo-Ho
authors.initials: JH
authors.lastname: Chung
mesh_terms: 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
chemical_list: 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