Document Detail

Bcl-2 is a negative regulator of interleukin-1beta secretion in murine macrophages in pharmacological-induced apoptosis.
MedLine Citation:
PMID:  20649584     Owner:  NLM     Status:  MEDLINE    
BACKGROUND AND PURPOSE: Cucurbitacin R, a natural anti-inflammatory product, has been shown to exhibit activity against both adjuvant-induced arthritis and delayed-type hypersensitivity reactions induced by various agents. Previous studies have demonstrated that the effects of cucurbitacin R stem from its inhibition of both cytokine production and lymphocyte proliferation.
EXPERIMENTAL APPROACHES: Effects of cucurbitacin R were investigated on lipopolysaccharide-stimulated RAW 264.7 cells. Cell cycle evolution was analysed by flow cytometry, detection of apoptosis by DNA ladder, Bcl-2, p21, p53, Bax, cleaved caspase-1 (p10), caspase-9, and caspase-3, cleaved caspase (p17) and interleukin-1beta detection was followed by Western blot analysis and mRNA expression with quantitative real time reverse transcription-polymerase chain reaction (qRT-PCR).
KEY RESULTS: Cucurbitacin R was found to induce apoptosis in lipopolysaccharide-stimulated RAW 264.7 macrophages through the inhibition of Bcl-2 expression, which regulates pro-inflammatory caspase-1 activation and interleukin-1beta release. Also, cucurbitacin R arrested the cell cycle in the G(2)/M phase and increased the subG(0) population in lipopolysaccharide-stimulated RAW 264.7 macrophages. Moreover, it increased the expression of proteins p53 and p21, down-regulated the expression of Bcl-2, activated the activity of caspase-1 and augmented the production of interleukin-1beta. Finally, the transfection of RAW 264.7 macrophages with a Bcl-2 expression plasmid produced the inhibition of apoptosis and caspase-1 activation/interleukin-1beta release induced by cucurbitacin R in RAW 264.7 cells.
CONCLUSIONS AND IMPLICATIONS: Taken together, these results point to a new apoptotic process in which interleukin-1beta release is directly regulated by Bcl-2 status; this contributes to the evidence that apoptotic processes do not induce inflammation.
J M Escandell; M C Recio; R M Giner; S Máñez; J L Ríos
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of pharmacology     Volume:  160     ISSN:  1476-5381     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-07-23     Completed Date:  2010-11-30     Revised Date:  2011-08-25    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1844-56     Citation Subset:  IM    
Departament de Farmacologia, Facultat de Farmàcia, Universitat de València, Burjassot, Spain.
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MeSH Terms
Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
Apoptosis / drug effects*,  immunology
Blotting, Western
Caspase 1 / genetics,  metabolism
Caspase 3 / metabolism
Cell Cycle / drug effects
Cell Line
Flow Cytometry
Interleukin-1beta / secretion*
Lipopolysaccharides / pharmacology
Macrophages / drug effects*,  immunology,  metabolism,  pathology
Membrane Potential, Mitochondrial / drug effects
Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors,  biosynthesis*,  genetics
RNA, Small Interfering / genetics
Reverse Transcriptase Polymerase Chain Reaction
Triterpenes / pharmacokinetics*
Reg. No./Substance:
0/Anti-Inflammatory Agents, Non-Steroidal; 0/Interleukin-1beta; 0/Lipopolysaccharides; 0/Proto-Oncogene Proteins c-bcl-2; 0/RNA, Small Interfering; 0/Triterpenes; 0/cucurbitacin R; EC 3.4.22.-/Caspase 3; EC 1

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