Inhibitory effects of 2,6-di-O-methyl-alpha-cyclodextrin on poly I:C signaling in macrophages.
In the present study, we examined the effects of alpha-cyclodextrin (alpha-CyD), 2-hydroxypropyl-alpha-cyclodextrin (HP-alpha-CyD) and 2,6-di-O-methyl-alpha-cyclodextrin (DM-alpha-CyD) on the nitric oxide (NO) and interferon-beta (IFN-beta) production in murine and human macrophages stimulated with Poly I:C and CpG-DNA, toll-like receptor 3 (TLR3) and TLR9 ligands, respectively. DM-alpha-CyD significantly inhibited NO production in RAW264.7 cells and U937 cells differentiated by phorbol myristate acetate (PMA), murine and human macrophage-like cell lines, respectively, stimulated with Poly I:C without cytotoxicity, but neither alpha-CyD nor HP-alpha-CyD did. Meanwhile, the three alpha-CyDs did not inhibit NO production in RAW264.7 cells stimulated with CpG-DNA. DM-alpha-CyD inhibited inducible NO synthase (iNOS) and IFN-beta expression upon stimulation with Poly I:C. Furthermore, DM-alpha-CyD markedly decreased the cellular uptake of Poly I:C in RAW264.7 cells. Therefore, DM-alpha-CyD may be useful as a potent inhibitor for excess activation of macrophages stimulated with Poly I:C.
Motoyama
Keiichi
K
Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan.
Hashimoto
Yosuke
Y
Hirayama
Fumitoshi
F
Uekama
Kaneto
K
Arima
Hidetoshi
H
D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D016899:Interferon-beta / Q000235:genetics; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D009844:Oligosaccharides / Q000494:pharmacology; D011070:Poly I-C / Q000378:metabolism* / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D047391:alpha-Cyclodextrins / Q000494:pharmacology*
C402302:(2-hydroxypropyl)-alpha-cyclodextrin; C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides; D009844:Oligosaccharides; D047391:alpha-Cyclodextrins; C479660:dimethyl-alpha-cyclodextrin; D009569:Nitric Oxide; D016899:Interferon-beta; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D011070:Poly I-C