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Immunological tolerance in a mouse model of immune-mediated liver injury induced by 16,16 dimethyl PGE2 and PGE2-containing nanoscale hydrogels

Paper ID Volume ID Publish Year Pages File Format Full-Text
7563 556 2011 11 PDF Available
Title
Immunological tolerance in a mouse model of immune-mediated liver injury induced by 16,16 dimethyl PGE2 and PGE2-containing nanoscale hydrogels
Abstract

Although immunosuppressive agents play a pivotal role in the success of organ transplantation, chronic toxicity has been a major issue for long-term treatment. The development of therapies that induce donor-specific immunological tolerance remains an important clinical challenge. In the present study, we investigated the underlying mechanisms and applications of prostaglandin (PG) E2 for the induction of immunological tolerance in mice with concanavalin A(Con A)-induced immune-mediated liver injury. The immunological tolerogenic effect of 16,16 dimethyl PGE2 (dmPGE2) pretreatment in C57B/6 male mice with Con A-induced liver injury was observed, and it was revealed that its response was partially associated with the expression of interleukin (IL)-10, an anti-inflammatory cytokine, in Kupffer cells. To apply native eicosanoids of PGE2 for tolerance induction in vivo, PGE2 was incorporated into l-lactic acid oligomer-grafted pullulan of an amphiphilic polymer to form a nano-sized hydrogel (PGE2-nanogel). Pharmacokinetics studies revealed that nanogel incorporation enabled PGE2 to have a prolonged life-time in circulating blood, and a tolerogenic effect was also observed in Con A-induced liver injury, the same as with dmPGE2 pretreatment. Nanogel-based prostaglandin administration might be developed as a therapeutic agent to induce immunological tolerance, which is necessary in allogenic organ and cell transplantation.

Keywords
Liver; Immunological tolerance; PGE2; Nanoparticle (nanogel)PG, (Prostaglandin); PGE2, (Prostaglandin E2); dmPGE2 16, (16 dimethyl PGE2); PGI2, (Prostaglandin I2); Con A, (Concanavalin A); IL, (Interleukin); IFN-γ, (interferon-γ); TNF-α, (tumor necrosis f
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Immunological tolerance in a mouse model of immune-mediated liver injury induced by 16,16 dimethyl PGE2 and PGE2-containing nanoscale hydrogels
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 32, Issue 21, July 2011, Pages 4925–4935
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