RRC ID 56106
Author Hoshi K, Yamazaki T, Yoshikawa C, Tsugawa W, Ikebukuro K, Sode K.
Title Synthesis of a hemin-containing copolymer as a novel immunostimulator that induces IFN-gamma production.
Journal Int J Nanomedicine
Abstract Background:Hemozoin, a chemical analog of a malarial pigment, is a crystal composed of heme dimers that can act as a potent Th1-type adjuvant, which strongly induces antibody production. However, the clinical applications of malarial hemozoin have limitations due to biosafety concerns and difficulties in the manufacturing process. Based on the premise that an analog of the heme polymer might display immunostimulatory effects, a hemin-containing polymer was developed as a novel immunostimulator.
Materials and methods:To synthesize the copolymer containing hemin and N-isopropylacrylamide (NIPAM), this study employed a conventional radical polymerization method using 2,2'-azodiisobutyronitrile as the radical initiator; the synthesized copolymer was designated as NIPAM-hemin.
Results:NIPAM-hemin was soluble and showed no cytotoxicity in vitro. The NIPAM-hemin copolymer induced the production of interferon (IFN)-γ and interleukin (IL)-6 from peripheral blood mononuclear cells, although hemin and the NIPAM monomer individually did not induce the production of any cytokines. The production of IFN-γ induced by NIPAM-hemin was independent of toll-like receptor 9 and the NLRP3 inflammasome pathway.
Conclusion:Given that NIPAM-hemin induced IL-6 and IFN-γ production in immune cells without any cytotoxic effects, NIPAM-hemin has potential therapeutic applications as a Th1-type adjuvant.
Volume 13
Pages 4461-4472
Published 2018-8-2
DOI 10.2147/IJN.S166259
PII ijn-13-4461
PMID 30122920
PMC PMC6080671
MeSH Acrylic Resins / chemical synthesis Acrylic Resins / chemistry Cell Death / drug effects Cell Line Hemin / pharmacology* Humans Immunologic Factors / pharmacology* Interferon-gamma / biosynthesis* Interleukin-6 / biosynthesis NF-kappa B / metabolism Polymers / chemical synthesis* Polymers / chemistry Signal Transduction / drug effects Spectrophotometry, Ultraviolet Spectroscopy, Fourier Transform Infrared Toll-Like Receptors / metabolism
IF 4.471
Times Cited 0
Resource
Human and Animal Cells RAW 264(RCB0535)