Melittin enhances apoptosis through suppression of IL-6/sIL-6R complex-induced NF-kappa B and STAT3 activation and Bcl-2 expression for human fibroblast-like synoviocytes in rheumatoid arthritis
- Title
- Melittin enhances apoptosis through suppression of IL-6/sIL-6R complex-induced NF-kappa B and STAT3 activation and Bcl-2 expression for human fibroblast-like synoviocytes in rheumatoid arthritis
- Other Titles
- sIL-6R complex-induced NF-kappa B and STAT3 activation and Bcl-2 expression for human fibroblast-like synoviocytes in rheumatoid arthritis
- Author
- 유대현
- Keywords
- Melittin; Synoviocyte; Apoptosis; STAT3; NF-kappa B; IL-6; COLLAGEN-INDUCED ARTHRITIS; BEE VENOM; SYNOVIAL FIBROBLASTS; MEDIATOR GENERATION; JOINT DESTRUCTION; CONTROLLED-TRIAL; IL-6 RECEPTOR; INTERLEUKIN-6; CELLS; INFLAMMATION
- Issue Date
- 2011-10
- Publisher
- ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER, 23 RUE LINOIS, 75724 PARIS, FRANCE
- Citation
- JOINT BONE SPINE, 78 (5), 471-477
- Abstract
- Objective: Resistance to apoptosis of fibroblast-like synoviocytes (FLS) is considered as a major characteristic in RA. This study was designed to identify whether melittin has a pro-apoptotic effect in IL-6/sIL6R-stimulated human FLS by investigating the expression of mitochondrial apoptosis-related genes, nuclear factor-kappa B (NF-kappa B), and signal transducer and activators of transcription (STAT) activation.Methods: Cell viability was determined using a MTT assay after melittin treatment. Expressions of STAT3 and mitochondrial apoptosis-related genes induced by the IL-6/sIL-6R complex were determined by real time-polymerase chain reaction and western blotting. The expression of NF-kappa B p65 following IL-6 stimulation was determined by western blot analysis. The effects of melittin on the expression of apoptosis-related genes and the transcription factors NF-kappa B p65 and STAT3 were assessed in FLS. Apoptosis of FLS was determined by TUNEL-labeling to detect DNA strand breaks and DNA fragmentation assays. Caspase-3 activity was determined by a colorimetric assay.Results: IL-6/sIL-6R induced the activation of the transcription factors, STAT3, NF-kappa B p65 (nucleus), and Bcl-2. Melittin increased the expression of pro-apoptosis-related molecules, namely caspase-3, caspase-9, Apaf-1, and cytosolic cytochrome c, in a dose-dependent manner after treatment with IL-6/sIL-6R. Melittin inhibited STAT3 activation, translocation of NF-kappa B p65 into the nucleus, and expression of anti-apoptotic genes such as Bcl-2 and mitochondrial cytochrome c.Conclusions: The pro-apoptotic effects of melittin likely result from inhibition of the activation of the transcription factors, STAT3 and NF-kappa B p65, and regulation of mitochondrial apoptosis-related genes. Melittin is thus a promising therapeutic option for RA as it induces apoptosis in apoptosis-resistant synoviocytes. (C) 2011 Societe francaise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.
- URI
- http://www.sciencedirect.com/science/article/pii/S1297319X11000054?_rdoc=1&_fmt=high&_origin=gateway&_docanchor=&md5=b8429449ccfc9c30159a5f9aeaa92ffb
- ISSN
- 1297-319X
- DOI
- 10.1016/j.jbspin.2011.01.004
- Appears in Collections:
- COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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