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The promotion of type 1 T helper cell responses to cationic polymers in vivo via toll-like receptor-4 mediated IL-12 secretion

Paper ID Volume ID Publish Year Pages File Format Full-Text
7937 570 2010 9 PDF Available
Title
The promotion of type 1 T helper cell responses to cationic polymers in vivo via toll-like receptor-4 mediated IL-12 secretion
Abstract

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-α 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.

Keywords
Cationic polymers; Th1 responses; IL-12; Toll-like receptor-4
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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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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 31, Issue 32, November 2010, Pages 8172–8180
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us