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.
Jin
Miao
M
Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan. jinmiaollh@hotmail.com
Iwamoto
Taku
T
Yamada
Kiyoshi
K
Satsu
Hideo
H
Totsuka
Mamoru
M
Shimizu
Makoto
M
D000818:Animals; D002457:Cell Extracts; D002460:Cell Line; D002809:Chondroitin Sulfates / Q000737:chemistry*; D002850:Chromatography, Gel; D015226:Dinucleoside Phosphates / Q000494:pharmacology*; D004187:Disaccharides / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D053592:Interleukin-1 Receptor-Associated Kinases / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D055666:Lipopeptides / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D010587:Phagocytosis / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000378:metabolism
D002457:Cell Extracts; D002809:Chondroitin Sulfates; D015226:Dinucleoside Phosphates; D004187:Disaccharides; D053592:Interleukin-1 Receptor-Associated Kinases; D015850:Interleukin-6; D055666:Lipopeptides; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D051217:Toll-Like Receptor 9; C508075:Pam(3)CSK(4) peptide; C015772:CpG dinucleotide; C507769:Irak1 protein, mouse