Disaccharide derived from chondroitin sulfate A suppressed CpG-induced IL-6 secretion in macrophage-like J774.1 cells

Interleukin (IL)-6 secretion from macrophage cells is known to be induced by toll-like receptor (TLR) 9 ligands, CpG (microbial DNA sequences containing unmethylated CpG dinucleotides). We have found, using macrophage-like J774.1 cells, that this induction was dramatically suppressed by a disaccharide derived from chondroitin sulfate A (Di-4S), but not by chondroitin sulfate A (CS-A) itself. The suppression of IL-6 secretion by Di-4S occurred at protein and mRNA expression levels. Di-4S inhibited the degradation of interleukin-1 receptor-associated kinase 1 (IRAK1) in the signaling pathway mediated by myeloid differentiation primary response gene (88) (MyD88) when stimulated by TLR9 activation. In addition to suppressing IRAK1 activation, interference with CpG–TLR9 interaction by Di-4S is also suggested to be one of the mechanisms. Oligosaccharides derived from chondroitin sulfates would be effective suppressing agents for the TLR9-mediated inflammation reaction.