Inhibitory effects of 2,6-di-O-methyl-α-cyclodextrin on Poly I:C signaling in macrophages

In the present study, we examined the effects of α-cyclodextrin (α-CyD), 2-hydroxypropyl-α-cyclodextrin (HP-α-CyD) and 2,6-di-O-methyl-α-cyclodextrin (DM-α-CyD) on the nitric oxide (NO) and interferon-β (IFN-β) production in murine and human macrophages stimulated with Poly I:C and CpG-DNA, toll-like receptor 3 (TLR3) and TLR9 ligands, respectively. DM-α-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 α-CyD nor HP-α-CyD did. Meanwhile, the three α-CyDs did not inhibit NO production in RAW264.7 cells stimulated with CpG-DNA. DM-α-CyD inhibited inducible NO synthase (iNOS) and IFN-β expression upon stimulation with Poly I:C. Furthermore, DM-α-CyD markedly decreased the cellular uptake of Poly I:C in RAW264.7 cells. Therefore, DM-α-CyD may be useful as a potent inhibitor for excess activation of macrophages stimulated with Poly I:C.