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
- Authors
- Kim, Seong-Kyu; Park, Ki-Yeun; Yoon, Wern-Chan; Park, Sung-Hoon; Park, Kwan-Kyu; Yoo, Dae-Hyun; Choe, Jung-Yoon
- Issue Date
- Oct-2011
- Publisher
- ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
- Keywords
- Melittin; Synoviocyte; Apoptosis; STAT3; NF-kappa B; IL-6
- Citation
- JOINT BONE SPINE, v.78, no.5, pp.471 - 477
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOINT BONE SPINE
- Volume
- 78
- Number
- 5
- Start Page
- 471
- End Page
- 477
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/167495
- DOI
- 10.1016/j.jbspin.2011.01.004
- ISSN
- 1297-319X
- 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.
- Files in This Item
-
Go to Link
- Appears in
Collections - 서울 의과대학 > 서울 내과학교실 > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/167495)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.