A human microsatellite DNA-mimicking oligodeoxynucleotide with CCT repeats negatively regulates TLR7/9-mediated innate immune responses via selected TLR pathways.

Abstract

A human microsatellite DNA-mimicking ODN (MS ODN) composed of CCT repeats, designated as SAT05f, has been studied for its capacity of negatively regulating innate immunity induced by TLR7/TLR9 agonists in vitro and in mice. The result showed that SAT05f could down-regulate TLR7/9-dependent IFN-alpha production in cultured human PBMC stimulated by inactivated Flu virus PR8 or HSV-1 or CpG ODN or imiquimod, protect d-GalN-treated mice from lethal shock induced by TLR9 agonist, not by TLR3/4 agonist. In addition, SAT05f significantly inhibit IFN-alpha production from purified human plasmacytoid cells (pDCs) stimulated by CpG ODN. Interestingly, SAT05f could up-regulate CD80, CD86, and HLA-DR on the pDCs in vitro, implying that SAT05f-mediated inhibition on IFN-alpha production could be related to the activation of pDCs. The data suggest that SAT05f could be developed as a candidate medicament for the treatment of TLR7/9 activation-associated diseases by inhibiting TLR7/9 signaling pathways.

• Authors: Ran Sun, Luguo Sun, Musheng Bao, Yongsheng Zhang, Li Wang, Xiuli Wu, Dali Hu, Yongjun Liu, Yongli Yu, Liying Wang
• Journal: Clinical immunology (Orlando, Fla.) (Clin Immunol) Vol. 134 Issue 3 Pg. 262-76 (Mar 2010) ISSN: 1521-7035 [Electronic] United States
• PMID: 20034855 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: 2009 Elsevier Inc. All rights reserved.

Chemical References

• Interferon-alpha
• Membrane Glycoproteins
• Oligodeoxyribonucleotides
• Tlr7 protein, mouse
• Tlr9 protein, mouse
• Toll-Like Receptor 7
• Toll-Like Receptor 9

Topics

• Animals
• Chlorocebus aethiops
• DNA Virus Infections (immunology, virology)
• Dendritic Cells (immunology)
• Dogs
• Enzyme-Linked Immunosorbent Assay
• Female
• Flow Cytometry
• Humans
• Immunity, Innate (immunology)
• Interferon-alpha (biosynthesis, immunology)
• Kaplan-Meier Estimate
• Membrane Glycoproteins (agonists, antagonists & inhibitors, immunology)
• Mice
• Mice, Inbred BALB C
• Microsatellite Repeats (immunology)
• Oligodeoxyribonucleotides (genetics, immunology, pharmacology)
• RNA Virus Infections (immunology, virology)
• Random Allocation
• Specific Pathogen-Free Organisms
• Toll-Like Receptor 7 (agonists, antagonists & inhibitors, immunology)
• Toll-Like Receptor 9 (agonists, antagonists & inhibitors, immunology)
• Vero Cells