Abstract
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.
Keywords: Intracellular trafficking, immunosuppression, oligodeoxynucleotide, toll-like receptor 9.
Current Pharmaceutical Biotechnology
Title:An Oligodeoxynucleotide with CCT Repeats Restrains CpG ODN-Induced TLR9 Trafficking
Volume: 15 Issue: 9
Author(s): Xiaoling Zhang, Wei Sun, Xiuli Wu, Hua Wang, Youyou Yan, Sheng Guo, Dandan Song, Hainan Li, Shuang Gao, Luowei Wang, Yongli Yu and Liying Wang
Affiliation:
Keywords: Intracellular trafficking, immunosuppression, oligodeoxynucleotide, toll-like receptor 9.
Abstract: 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.
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Cite this article as:
Zhang Xiaoling, Sun Wei, Wu Xiuli, Wang Hua, Yan Youyou, Guo Sheng, Song Dandan, Li Hainan, Gao Shuang, Wang Luowei, Yu Yongli and Wang Liying, An Oligodeoxynucleotide with CCT Repeats Restrains CpG ODN-Induced TLR9 Trafficking, Current Pharmaceutical Biotechnology 2014; 15 (9) . https://dx.doi.org/10.2174/1389201015666141031114708
DOI https://dx.doi.org/10.2174/1389201015666141031114708 |
Print ISSN 1389-2010 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4316 |
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