Document Detail


In vitro and in vivo transfection of p21 gene enhances cyclosporin A-mediated inhibition of lymphocyte proliferation.
MedLine Citation:
PMID:  10925268     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cyclosporine has potent antiproliferative properties, some of which may be via the induction of the cyclin inhibitor p21. In this study, we describe the effects of in vitro and in vivo transfection of p21 in lymphoid and nonlymphoid cells. For in vitro studies, p21 sense plasmid DNA was transfected in A-549 cells (lung adenocarcinoma cell line) and Jurkat cells (human lymphoid cell line). This in vitro transfection of p21 resulted in the inhibition of spontaneous and mitogen-induced cellular proliferation ([3H]thymidine uptake) and also augmented the antiproliferative effects of cyclosporine. In vivo transfection of p21 was accomplished in mice via the i.m. injection of p21 sense plasmid DNA complexed with cationic lipids. As was the case in the cell lines, p21 mRNA was augmented in heart, lung, liver, and spleen 7 days after i.m. injection of p21 sense plasmid DNA. The mitogen (anti-CD3)-induced proliferation of splenocytes from p21-overexpressing mice was significantly decreased, and again this effect was augmented by cotreatment with cyclosporine. These novel findings demonstrate the potential of targeting the cell cycle directly to inhibit alloimmune activation in organ transplantation. This may serve as an alternate strategy to induce immunosuppression, perhaps with less toxicity than that which is seen with conventional immunosuppressive agents.
Authors:
A K Khanna; J D Hosenpud
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  165     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  2000 Aug 
Date Detail:
Created Date:  2000-09-14     Completed Date:  2000-09-14     Revised Date:  2006-05-01    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1882-8     Citation Subset:  AIM; IM    
Affiliation:
The Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA. akkhanna@mcw.edu
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MeSH Terms
Descriptor/Qualifier:
Adjuvants, Immunologic / administration & dosage*,  genetics*
Animals
Cyclin-Dependent Kinase Inhibitor p21
Cyclins / administration & dosage*,  biosynthesis,  genetics*,  physiology
Cyclosporine / pharmacology*
Gene Expression Regulation / immunology
Growth Inhibitors / pharmacology
Humans
Immunosuppressive Agents / pharmacology*
Injections, Intramuscular
Jurkat Cells
Kidney / metabolism
Liver / metabolism
Lymphocyte Activation / drug effects*,  genetics,  immunology
Mice
Myocardium / metabolism
Organ Specificity / genetics,  immunology
Plasmids / administration & dosage,  chemical synthesis,  immunology
Spleen / cytology,  immunology,  metabolism
Transfection / immunology*
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
0/Adjuvants, Immunologic; 0/CDKN1A protein, human; 0/Cdkn1a protein, mouse; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Cyclins; 0/Growth Inhibitors; 0/Immunosuppressive Agents; 59865-13-3/Cyclosporine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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