Journal
IMMUNOLOGY LETTERS
Volume 183, Issue -, Pages 52-61Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.imlet.2017.01.015
Keywords
SIGIRR; Nanoparticles; TLRs; Colitis
Categories
Funding
- National Natural Science Foundation of China [30860109, 81502472]
- Jiangxi Provincial Natural Science Fund [20142BAB205044]
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Background: Inflammatory bowel disease (IBD) is characterized by uncontrolled immune responses in inflamed mucosa, especially the TLR (Toll-like receptor) signaling pathway. Single Ig domain containing IL-1 receptor-related molecule (SIGIRR), a negative regulator of the TLR signaling pathway, whether had a therapeutic effect in a mouse model of IBD, and the underlying mechanism has not been investigated. Methods: Coacervation was used to prepare chitosan/pUNO-SIGIRR nanoparticles. The nanoparticles were administered to mice with colitis using enteroclysis. The disease activity index (DAI) and hematoxylin and eosin staining (HE) staining were used to evaluate the therapeutic effects of the SIGIRR nanoparticles. Immunohistochemistry was performed to elucidate the underlying mechanism driving these effects. Results: Chitosan/pUNO-SIGIRR nanoparticles were successfully constructed and were spherical, with a mean diameter of less than 100 nm, and the plasmid encapsulating efficiency was 99.9%. The chitosan/pUNO-SIGIRR nanoparticles attenuated colonic tissue inflammation through the inhibition of TLR4/NF-kappa B overactivation by downregulating TLR4, MyD88 and NF-kappa B p65 expression in a mouse model of colitis. Conclusions: The novel chitosan/pUNO-SIGIRR nanoparticles had a therapeutic effect on IBD in a mouse model through the inhibition of TLR4/NF-kappa B overactivation. (C) 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.
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