An oligodeoxynucleotide with CCT repeats restrains CpG ODN-induced TLR9 trafficking.
Toll-like receptor 9 (TLR9) can sense pathogen DNA and CpG ODN or even self-DNA by trafficking assisted by Unc93B1, an endoplasmic reticulum (ER) transmembrane protein, from ER to endolysosomes or cell surface. In previous study, we found that an oligodeoxynucleotide with CCT repeats (SAT05f) could selectively inhibit TLR7/9 activation. However, the mechanism for the inhibitory activity of SAT05f is still unknown. In present research, it was found that SAT05f could inhibit CpG ODN-induced the intracellular trafficking of TLR9 and Unc93B1 with feedback the responses of decreased surface TLR9 and enhanced TLR9 mRNA expression but not influence TLR9 protein level by using human plasmacytoid dendritic cell line CAL-1 cells, suggesting that SAT05f inhibits TLR9 activation by restraining TLR9 trafficking. Since the mitochondrial DNA released from injured tissue can cause systemic inflammatory response syndrome (SIRS), this study may provide valuable data for prevention and treatment of SIRS and rescue severe trauma patients.
Xiaoling
X
Zhang
Wei
W
Sun
Xiuli
X
Wu
Hua
H
Wang
Youyou
Y
Yan
Sheng
S
Guo
Dandan
D
Song
Hainan
H
Li
Shuang
S
Gao
Luowei
L
Wang
Yongli
Y
Yu
Department of Molecular Biology or Department of Immunology, College of Basic Medical Sciences, Jilin University, 126 N Xinmin Street, Changchun, Jilin 130021, China. wlying@jlu.edu.cn.
Liying
L
Wang
D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D050839:Interferon Regulatory Factor-7 / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics; D026901:Membrane Transport Proteins / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000819:agonists / Q000235:genetics / Q000378:metabolism*
C408982:CPG-oligonucleotide; C508609:IL10 protein, human; D050839:Interferon Regulatory Factor-7; D026901:Membrane Transport Proteins; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; C561797:SAT05f; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; C454130:UNC93B1 protein, human; D016753:Interleukin-10