| Immune regulatory effects of simvastatin on regulatory T cell-mediated tumour immune tolerance. | |
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MedLine Citation:
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PMID: 20491794 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Statins are potent inhibitors of hydroxyl-3-methylglutaryl co-enzyme A (HMG-CoA) reductase, and have emerged as potential anti-cancer agents based on preclinical evidence. In particular, compelling evidence suggests that statins have a wide range of immunomodulatory properties. However, little is known about the role of statins in tumour immune tolerance. Tumour immune tolerance involves the production of immunosuppressive molecules, such as interleukin (IL)-10, transforming growth factor (TGF)-beta and indoleamine-2,3-dioxygenase (IDO) by tumours, which induce a regulatory T cell (T(reg)) response. In this study, we investigated the effect of simvastatin on the production of IL-10, TGF-beta and IDO production and the proliferation of T(regs) using several cancer cell lines, and Lewis lung cancer (3LL) cells-inoculated mouse tumour model. Simvastatin treatment resulted in a decrease in the number of cancer cells (3LL, A549 and NCI-H292). The production of the immune regulatory markers IL-10, TGF-beta in 3LL and NCI-H292 cells increased after treatment with simvastatin. The expression of IDO and forkhead box P3 (FoxP3) transcription factor was also increased in the presence of simvastatin. In a murine 3LL model, there were no significant differences in tumour growth rate between untreated and simvastatin-treated mice groups. Therefore, while simvastatin had an anti-proliferative effect, it also exhibited immune tolerance-promoting properties during tumour development. Thus, due to these opposing actions, simvastatin had no net effect on tumour growth. |
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Authors:
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K J Lee; J Y Moon; H K Choi; H O Kim; G Y Hur; K H Jung; S Y Lee; J H Kim; C Shin; J J Shim; K H In; S H Yoo; K H Kang; S Y Lee |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-05-18 |
Journal Detail:
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Title: Clinical and experimental immunology Volume: 161 ISSN: 1365-2249 ISO Abbreviation: Clin. Exp. Immunol. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-07-26 Completed Date: 2010-08-27 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 0057202 Medline TA: Clin Exp Immunol Country: England |
Other Details:
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Languages: eng Pagination: 298-305 Citation Subset: IM |
Affiliation:
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Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Count Cell Cycle / drug effects Cell Line, Tumor Cell Proliferation / drug effects Cyclin D1 / metabolism Cytostatic Agents / pharmacology, therapeutic use Forkhead Transcription Factors / genetics Gene Expression / drug effects, genetics Humans Immune Tolerance / drug effects*, immunology Immunosuppressive Agents / pharmacology, therapeutic use Indoleamine-Pyrrole 2,3,-Dioxygenase / genetics Interleukin-10 / metabolism Interleukin-2 Receptor alpha Subunit / metabolism Mice Mice, Inbred C57BL Neoplasms / drug therapy, immunology*, metabolism, pathology Simvastatin / pharmacology*, therapeutic use Spleen / cytology, immunology T-Lymphocytes, Regulatory / cytology, drug effects*, immunology, metabolism Transforming Growth Factor beta / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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R13 HD055720-01/HD/NICHD NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Ccnd1 protein, mouse; 0/Cytostatic Agents; 0/Forkhead Transcription Factors; 0/Foxp3 protein, mouse; 0/Il2ra protein, mouse; 0/Immunosuppressive Agents; 0/Interleukin-2 Receptor alpha Subunit; 0/Transforming Growth Factor beta; 130068-27-8/Interleukin-10; 136601-57-5/Cyclin D1; 79902-63-9/Simvastatin; EC 1.13.11.42/Indoleamine-Pyrrole 2,3,-Dioxygenase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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