title: Toll-like receptor agonists and alpha-galactosylceramide synergistically enhance the production of interferon-gamma in murine splenocytes.
abstract: Vα14 natural killer T (iNKT) cells activated by alpha-galactosylceramide (GalCer) secrete a large amount of cytokines. Toll-like receptors (TLRs) play a critical role in the innate immune responses via the recognition of pathological antigen. Previously we demonstrated that the iNKT cells activated by GalCer augmented LPS-induced NO production in peritoneal cells. In this study, we examined the effect of GalCer and TLR agonists by IFN-γ production from splenocytes. Splenocytes pretreated with GalCer induced TLR3, 4, 7/8, and 9 agonists in vitro, resulting in the enhancement of IFN-γ mRNA expression. In particular, IFN-γ stimulated by GalCer and LPS was increased in NK cells and CD8 T cells, and inhibited by a neutralizing anti-IL-12 antibody. Pretreatment with GalCer enhanced the phosphorylation of IκB-α induced by LPS stimulation. The present study showed that co-stimulation of GalCer and TLR agonists powerfully induced the production of IFN-γ from splenocytes.
authors.affiliation: Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ando
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Ito
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Ohtaki
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Seishima
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004357:Drug Synergism; D005699:Galactosylceramides / Q000494:pharmacology*; D007371:Interferon-gamma / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013154:Spleen / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D051193:Toll-Like Receptors / Q000819:agonists* / Q000378:metabolism*
chemical_list: D005699:Galactosylceramides; D051193:Toll-Like Receptors; C493154:alpha-galactosylceramide; D007371:Interferon-gamma