Synthetic Human TLR9-LRR11 Peptide Attenuates TLR9 Signaling by Binding to and thus Decreasing Internalization of CpG Oligodeoxynucleotides

Pan, Xichun; Li, Bin; Kuang, Mei; Liu, Xin; Cen, Yanyan; Qin, Rongxin; Ding, Guohui; Zheng, Jie; Zhou, Hong

doi:10.3390/ijms17020242

Cited by 7 publications

(7 citation statements)

References 30 publications

(57 reference statements)

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“… 2011 ; Cho and Hsieh 2016 ; Pan et al. 2016 ), we learned that the TLR9 ligand is a kind of CpG motif or synthetic CpG-ODN in bacterial and viral DNA. Through swallowing, CpG DNA enters the body, then binds with TLR9 and promotes dimerization; based on the TIR domain, dimerized TLR9 raises adapter molecules with myeloid differentiation factor 88 (MyD88) (Martin and Wesche 2002 ).…”

Section: Resultsmentioning

confidence: 99%

Ma Huang Tang ameliorates bronchial asthma symptoms through the TLR9 pathway

Jiao

Wang

et al. 2018

Pharmaceutical Biology

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Context: Ma Huang Tang (MHT) has been used to treat influenza, fever, bronchial asthma, etc. as a traditional Chinese medication. However, the anti-inflammation mechanism of MHT remains unclear.Objective: The study identifies the possible mechanisms of MHT on ovalbumin (OVA)-induced acute bronchial asthma in mice.Materials and methods: First, an asthma-related protein-protein interaction (PPI) network was constructed. And then, the acute bronchial asthma mice models were established by exposing to aerosolized 1% ovalbumin for 30 min/day for 1 week, and the mice were administered 2.0, 4.0, or 8.0 g/kg of MHT daily. To evaluate therapeutic effect, sensitization time, abdominal breathing time, eosinophils in bronchoalveolar lavage fluid, and tissue and trachea pathology were examined. Related genes were measured using RNA sequencing (RNA-seq). The expression levels of TLR9 in lung and trachea tissues were determined by immunohistochemical staining.Results: MHT had a LD50 = 19.2 g/kg against asthma, while MHT at high doses (8 g/kg) effectively extended the sensitization time and abdominal breathing time and alleviated OVA-induced eosinophilic airway inflammation and mitigated pathological changes. The RNA-seq assay showed that the high-dose MHT resulted in a significant decrease in the levels of TLR9, TRAF6, TAB2, etc. in the lung tissue. Immunohistochemical assay confirmed the down-regulated of TLR9. Molecular docking revealed that six MHT compounds potentially mediated the TLR9 signaling pathway.Discussion and conclusions: MHT could mitigate the pathological changes of acute asthma-like syndrome through inhibition of the TLR9 pathway. Results of this study may provide a reference for the development of a novel therapy for patients with allergic asthma.

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Section: Resultsmentioning

confidence: 99%

Ma Huang Tang ameliorates bronchial asthma symptoms through the TLR9 pathway

Jiao

Wang

et al. 2018

Pharmaceutical Biology

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“…According to the previous report, CpG ODN activates macrophages via TLR9 signaling. 10,11 Therefore, we F I G U R E 2 CpG ODN activated macrophage via regulating TLR9/MyD88/NF-κB pathway. A, The mRNA levels of IL-1β, IL-6, and TNF-α in macrophages with different treatments.…”

Section: Cpg Odn Activated Macrophage Via Regulating Tlr9/myd88/nf-κb Pathwaymentioning

confidence: 99%

A C‐type CpG ODN accelerates wound healing via regulating fibroblasts and immune response

Zuo

et al. 2018

J of Cellular Biochemistry

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Abolished or delayed wound healing is a serious problem in clinical surgery, therefore, the new therapy for wound healing is needed. Synthetic oligodeoxynucleotides containing one or more CpG motifs (CpG ODN) has been reported to activate the immune system and improves skin wound healing. The aim of the present study was to evaluate the role of a new C‐type CpG ODN in wound healing. We found that the CpG ODN promoted cell proliferation and collagen I production in human skin fibroblasts cells. Besides, we also investigated the effect of CpG ODN on the activation of immune cells. The macrophages and plasmacytoid dendritic cells (pDCs) were incubated with CpG ODN. CpG ODN activated macrophage and pDCs via regulating TLR9/MyD88/NF‐κB pathway and TLR9/MyD88/IRF7 pathway, respectively. To further evaluate the effect of CpG ODN on wound healing in vivo a wound healing model was established in mice. The results showed that CpG ODN treatment accelerated wound healing in mice. CpG ODN increased cytokines secretion in wound skin and elevated the ratio of CD4 + and CD8 + T cells in the spleen. Our results showed that CpG ODN accelerated wound healing, which was partly due to the regulation of fibroblasts and immune response. The findings suggested that the CpG ODN might be a proper medicament for the treatment of wound healing.

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“…This approach involved immobilizing a 5′-biotinylated ODN on the surface of TSM transducer covered by NeutrAvidin and then adding the LRR11 peptide. An unrelated peptide (URP) with a random primary structure (LQTLDLRDNALTTIHFIPSIPD) was used as a negative control [ 9 ]. The measurement procedure was divided into several steps, in which each immobilization stage was followed by washing with an appropriate buffer solution; when peptide solutions at different concentrations (from 1 to 100 nM) were added to the surface-modified TSM transducer, a wash with Hanks buffer was used before increasing the peptide concentration.…”

Section: Resultsmentioning

confidence: 99%

“…The crystal structure of TLR9 was analyzed [ 7 ] and it was predicted that leucine-rich repeats (LRRs) of this receptor are involved in DNA recognition. It was then experimentally shown that the LRR11 peptide derived from the TLR9 sequence can bind to the CpG-ODNs [ 8 ], which leads to an attenuating of TLR9 signaling and a decrease in the oligonucleotide internalization by a mouse-derived monocyte/macrophage cell line RAW 264.7 [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Magic Peptide: Unique Properties of the LRR11 Peptide in the Activation of Leukotriene Synthesis in Human Neutrophils

Viryasova

Golenkina

Hianik

et al. 2021

IJMS

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Neutrophil-mediated innate host defense mechanisms include pathogen elimination through bacterial phagocytosis, which activates the 5-lipoxygenase (5-LOX) product synthesis. Here, we studied the effect of synthetic oligodeoxyribonucleotides (ODNs), which mimic the receptor-recognized sites of bacterial (CpG-ODNs) and genomic (G-rich ODNs) DNAs released from the inflammatory area, on the neutrophil functions after cell stimulation with Salmonella typhimurium. A possible mechanism for ODN recognition by Toll-like receptor 9 (TLR9) and RAGE receptor has been proposed. We found for the first time that the combination of the magic peptide LRR11 from the leucine-rich repeat (LRR) of TLR9 with the CpG-ODNs modulates the uptake and signaling from ODNs, in particular, dramatically stimulates 5-LOX pathway. Using thickness shear mode acoustic method, we confirmed the specific binding of CpG-ODNs, but not G-rich ODN, to LRR11. The RAGE receptor has been shown to play an important role in promoting ODN uptake. Thus, FPS-ZM1, a high-affinity RAGE inhibitor, suppresses the synthesis of 5-LOX products and reduces the uptake of ODNs by neutrophils; the inhibitor effect being abolished by the addition of LRR11. The results obtained revealed that the studied peptide-ODN complexes possess high biological activity and can be promising for the development of effective vaccine adjuvants and antimicrobial therapeutics.

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Synthetic Human TLR9-LRR11 Peptide Attenuates TLR9 Signaling by Binding to and thus Decreasing Internalization of CpG Oligodeoxynucleotides

Cited by 7 publications

References 30 publications

Ma Huang Tang ameliorates bronchial asthma symptoms through the TLR9 pathway

Ma Huang Tang ameliorates bronchial asthma symptoms through the TLR9 pathway

A C‐type CpG ODN accelerates wound healing via regulating fibroblasts and immune response

Magic Peptide: Unique Properties of the LRR11 Peptide in the Activation of Leukotriene Synthesis in Human Neutrophils

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