Treating Autoimmune Inflammatory Diseases with an siERN1-Nanoprodrug That Mediates Macrophage Polarization and Blocks Toll-like Receptor Signaling

ACS Nano ◽  
2021 ◽  
Author(s):  
Naibo Feng ◽  
Li Liang ◽  
Mengtian Fan ◽  
Yu Du ◽  
Cheng Chen ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Macrophage Polarization ◽  
Receptor Signaling ◽  
Toll Like Receptor

scholarly journals Toll-Like Receptor 9 Inactivation Alleviated Atherosclerotic Progression and Inhibited Macrophage Polarized to M1 Phenotype in ApoE−/−Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Chunmei Ma ◽  
Qiufang Ouyang ◽  
Ziyang Huang ◽  
Xiaoqing Chen ◽  
Ye Lin ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Macrophage Polarization ◽  
Immunohistochemical Analysis ◽  
Plaque Burden ◽  
Toll Like Receptor ◽  
Plaque Vulnerability ◽  
M1 Phenotype ◽  
Functional Inactivation ◽  
Atherosclerosis Development

Objective. Toll-like receptor 9 (TLR9) is involved in many inflammatory diseases, but its role in atherosclerosis remains controversial. This study aimed to investigate the role of TLR9 in atherosclerosis development and macrophage polarization.Methods. ApoE−/−mice were treated with vehicle or IRS869 for 12 weeks. Plaque vulnerability was assessed with immunohistochemical analysis, picro-sirius red, and oil red O staining. The expressions of M1- and M2-associated markers in plaques were detected by RT-PCR and immunofluorescence. The aorta TLR9 and its downstream molecules including myeloid differentiation protein 88 (MyD88), phosphorylated nuclear factor-kappa B (p-NF-κB), and interferon regulatory factor 7 (IRF7) were determined by western blot analysis. The frequency of M1 and M2 subtype in RAW264.7 cells treated with IRS869 and/or ODN1826 was evaluated with flow cytometry.Results. In ApoE−/−mice, functional inactivation of TLR9 pathway resulted in attenuated atherosclerosis development, as manifested by reduced plaque burden and by decreased plaque vulnerability. Mechanistically, TLR9 inhibition prevented the activation of MyD88/NF-κB pathway and shifted the balance of M1/M2 toward M2 macrophages that were involved.Conclusions. Our data indicated that TLR9 inactivation ameliorated atherosclerosis via skewing macrophage plasticity to M2 phenotype in ApoE-deficient mice. These findings may provide a promising therapeutic strategy for atherosclerosis.

The essential roles of Toll-like receptor signaling pathways in sterile inflammatory diseases

2011 ◽  
Vol 11 (10) ◽  
pp. 1422-1432 ◽  
Author(s):  
Qing Lin ◽  
Mingcai Li ◽  
Dan Fang ◽  
Jiazhu Fang ◽  
Shao Bo Su
Keyword(s):  
Signaling Pathways ◽  
Inflammatory Diseases ◽  
Receptor Signaling ◽  
Toll Like Receptor

scholarly journals Targeting Toll-Like Receptor 2: Polarization of Porcine Macrophages by a Mycoplasma-Derived Pam2cys Lipopeptide

Vaccines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 692
Author(s):  
Giulia Franzoni ◽  
Antonio Anfossi ◽  
Chiara Grazia De Ciucis ◽  
Samanta Mecocci ◽  
Tania Carta ◽  
...  
Keyword(s):  
Mhc Class Ii ◽  
Macrophage Polarization ◽  
Surface Protein ◽  
Antimicrobial Activities ◽  
Toll Like Receptor ◽  
Activation Markers ◽  
Class I Mhc ◽  
Toll Like Receptor 2

Toll-like receptor 2 (TLR2) ligands are attracting increasing attention as prophylactic and immunotherapeutic agents against pathogens and tumors. We previously observed that a synthetic diacylated lipopeptide based on a surface protein of Mycoplasma agalactiae (Mag-Pam2Cys) strongly activated innate immune cells, including porcine monocyte-derived macrophages (moMΦ). In this study, we utilized confocal microscopy, flow cytometry, multiplex cytokine ELISA, and RT-qPCR to conduct a comprehensive analysis of the effects of scalar doses of Mag-Pam2Cys on porcine moMΦ. We observed enhanced expression of activation markers (MHC class I, MHC class II DR, CD25), increased phagocytotic activity, and release of IL-12 and proinflammatory cytokines. Mag-Pam2Cys also upregulated the gene expression of several IFN-α subtypes, p65, NOS2, and molecules with antimicrobial activities (CD14, beta defensin 1). Overall, our data showed that Mag-Pam2Cys polarized porcine macrophages towards a proinflammatory antimicrobial phenotype. However, Mag-Pam2Cys downregulated the expression of IFN-α3, six TLRs (TLR3, -4, -5, -7, -8, -9), and did not interfere with macrophage polarization induced by the immunosuppressive IL-10, suggesting that the inflammatory activity evoked by Mag-Pam2Cys could be regulated to avoid potentially harmful consequences. We hope that our in vitro results will lay the foundation for the further evaluation of this diacylated lipopeptide as an immunopotentiator in vivo.

CgNrdp1, a conserved negative regulating factor of MyD88-dependent Toll like receptor signaling in oyster Crassostrea gigas

2018 ◽  
Vol 74 ◽  
pp. 386-392 ◽  
Author(s):  
Rui Sun ◽  
Limei Qiu ◽  
Qilin Yi ◽  
Mengqiang Wang ◽  
Feng Yue ◽  
...  
Keyword(s):  
Crassostrea Gigas ◽  
Receptor Signaling ◽  
Toll Like Receptor
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