| The promotion of type 1 T helper cell responses to cationic polymers in vivo via toll-like receptor-4 mediated IL-12 secretion. | |
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MedLine Citation:
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PMID: 20692033 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cationic polymers with nucleic acid drug delivery ability are widely used in experimental and clinical studies. However, their interactions with the immune systems are rarely studied. In the present study, cationic polymers including PEI, polylysine, cationic dextran and cationic gelatin exhibited strong stimulation on Th1 response which was characterized by the induction of the proliferation of CD4(+) T cells and the secretion of Th1 related cytokines. Experiments performed on macrophages demonstrated that cationic polymers specifically stimulated the macrophage to secrete IL-12 which is one of the main Th1-inducing cytokines. The result that MyD88 inhibitor remarkably reduced the IL-12 expression induced by cationic polymers suggested that this stimulation was mainly mediated by toll-like receptor (TLR) pathway. Additionally, cationic polymers could strongly inhibit LPS-induced TNF-alpha secretion in macrophages. This result implied that cationic polymers may interact with macrophages through TLR-4 which is the receptor of LPS. The following test of inhibiting IL-12 expression stimulated by cationic polymers using TLR-4 antibody proved that the stimulation was mainly mediated by TLR-4. Data in the present study demonstrated that the stimulation ability of cationic polymer was related with its cationic degree and neutralizing cationic polymer with anionic polymer completely abrogated the stimulation effect. The molecular weight of the polymers also influenced their stimulation ability, larger molecular means stronger stimulation ability. In conclusion, the present study revealed that cationic polymers could promote Th1 responses in vivo via TLR-4 mediated IL-12 secretion and the molecular weight and cationic degree of the polymers determined the stimulation ability. |
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Authors:
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Huan Chen; Pei Li; Yuan Yin; Xing Cai; Zhen Huang; Jiangning Chen; Lei Dong; Junfeng Zhang |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-08-09 |
Journal Detail:
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Title: Biomaterials Volume: 31 ISSN: 1878-5905 ISO Abbreviation: Biomaterials Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-09-06 Completed Date: 2011-01-04 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8100316 Medline TA: Biomaterials Country: England |
Other Details:
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Languages: eng Pagination: 8172-80 Citation Subset: IM |
Copyright Information:
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Copyright (c) 2010 Elsevier Ltd. All rights reserved. |
Affiliation:
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State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University 210093, PR China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Biocompatible Materials / metabolism* Cations / immunology Cell Differentiation Cell Line Cells, Cultured Dextrans / immunology Gelatin / immunology Interleukin-12 / immunology* Macrophages / immunology Male Mice Mice, Inbred C57BL Polyethyleneimine / metabolism Polylysine / immunology Polymers / metabolism* Spleen / cytology Th1 Cells / immunology* Toll-Like Receptor 4 / immunology* |
| Chemical | |
Reg. No./Substance:
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0/Biocompatible Materials; 0/Cations; 0/Polymers; 0/Toll-Like Receptor 4; 187348-17-0/Interleukin-12; 25104-18-1/Polylysine; 9000-70-8/Gelatin; 9002-98-6/Polyethyleneimine; 9004-54-0/Dextrans |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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