| Bcl-2 is a negative regulator of interleukin-1beta secretion in murine macrophages in pharmacological-induced apoptosis. | |
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MedLine Citation:
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PMID: 20649584 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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J M Escandell; M C Recio; R M Giner; S Máñez; J L Ríos |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: British journal of pharmacology Volume: 160 ISSN: 1476-5381 ISO Abbreviation: Br. J. Pharmacol. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-07-23 Completed Date: 2010-11-30 Revised Date: 2011-08-25 |
Medline Journal Info:
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Nlm Unique ID: 7502536 Medline TA: Br J Pharmacol Country: England |
Other Details:
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Languages: eng Pagination: 1844-56 Citation Subset: IM |
Affiliation:
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Departament de Farmacologia, Facultat de Farmàcia, Universitat de València, Burjassot, Spain. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals 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 Mice Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors, biosynthesis*, genetics RNA, Small Interfering / genetics Reverse Transcriptase Polymerase Chain Reaction Transfection Triterpenes / pharmacokinetics* |
| Chemical | |
Reg. No./Substance:
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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 3.4.22.36/Caspase 1 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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