Therapeutic effect of repeated natural killer T cell stimulation in mouse cholangitis complicated by colitis.
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 alpha-galactosylceramide. CD-1 mice were administered 2.0% dextran sulfate sodium for 29 days and injection of alpha-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. alpha-Galactosylceramide improved survival rate, weight gain, and inflammation score. Also, interferon-gamma 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 alpha-galactosylceramide has a therapeutic effect.
Numata
Yoshihiro
Y
Department of General Medicine and Clinical Pharmacotherapy, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
Tazuma
Susuma
S
Ueno
Yoshitaka
Y
Nishioka
Tomoji
T
Hyogo
Hideyuki
H
Chayama
Kazuaki
K
D000818:Animals; D015209:Cholangitis, Sclerosing / Q000209:etiology* / Q000473:pathology; D003092:Colitis / Q000209:etiology* / Q000473:pathology; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005699:Galactosylceramides / Q000008:administration & dosage / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018417:Th1 Cells / Q000502:physiology; D018418:Th2 Cells / Q000502:physiology
D005699:Galactosylceramides; C493154:alpha-galactosylceramide; D016264:Dextran Sulfate