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Therapeutic Effect of Repeated Natural Killer T Cell Stimulation in Mouse Cholangitis Complicated by Colitis
Authors:Yoshihiro?Numata,Susuma?Tazuma  author-information"  >  author-information__contact u-icon-before"  >  mailto:stazuma@hiroshima-u.ac.jp"   title="  stazuma@hiroshima-u.ac.jp"   itemprop="  email"   data-track="  click"   data-track-action="  Email author"   data-track-label="  "  >Email author,Yoshitaka?Ueno,Tomoji?Nishioka,Hideyuki?Hyogo,Kazuaki?Chayama
Affiliation:(1) Department of General Medicine and Clinical Pharmacotherapy, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan;(2) Department of General Medicine and Clinical Pharmacotherapy, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan
Abstract:Primary sclerosing cholangitis is often complicated by ulcerative colitis. Recently, we reported on Th1-dominant cholangitis associated with experimental colitis, and natural killer T (NKT) cells might play an important role in this model. The aim of this study was to clarify the immunopathogenic role of NKT cells in this model using α-galactosylceramide. CD-1 mice were administered 2.0% dextran sulfate sodium for 29 days and injection of α-galactosylceramide was performed every 5 days, then inflammation was assessed. Mononuclear cells from the liver were analyzed with respect to cytokine production and the surface marker. α -Galactosylceramide improved survival rate, weight gain, and inflammation score. Also, interferon-γ release from MNC, CD4/CD8 ratio, NKT cell population, and NK cell population were decreased by this treatment. These findings indicate that repeated stimulation of NKT cells modifies the Th1/Th2 balance to reduce Th1 dominance, and this may be a mechanism by which α -galactosylceramide has a therapeutic effect.
Keywords:primary sclerosing cholangitis  natural killer T cells  Th1  ulcerative colitis
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