scholarly journals Proteomic Analysis of HDAC3 Selective Inhibitor in the Regulation of Inflammatory Response of Primary Microglia

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Mingxu Xia ◽  
Qiuchen Zhao ◽  
He Zhang ◽  
Yanting Chen ◽  
Zengqiang Yuan ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Treated Group ◽  
Toll Like Receptor ◽  
Primary Microglia ◽  
Protein Mass ◽  
Protein Mass Spectrometry ◽  
Receptor Signaling Pathway ◽  
Toll Like Receptor 2 ◽  
Protein Alterations

HDAC3 has been shown to regulate inflammation. However, the role of HDAC3 in primary microglia is largely unknown. RGFP966 is a newly discovered selective HDAC3 inhibitor. In this study, we used protein mass spectrometry to analyze protein alterations in LPS-treated primary microglia with the application of RGFP966. Generally, about 2000 proteins were studied. 168 of 444 (37.8%) LPS-induced proteins were significantly reduced with the treatment of RGFP966, which mainly concentrated on Toll-like receptor signaling pathway. In this regard, we selected Toll-like receptor 2 (TLR2), TLR3, TLR6, MAPK p38, CD36, and spleen tyrosine kinase (SYK) for further validation and found that they were all significantly upregulated after LPS stimulation and downregulated in the presence of RGFP966. Additionally, RGFP966 inhibited supernatant tumor necrosis factor (TNF)-α and Interleukin 6 (IL-6) concentrations. Activation of STAT3 and STAT5 was partially blocked by RGFP966 at 2 h after LPS-stimulation. The fluorescence intensity of CD16/32 was significantly decreased in LPS + RGFP966-treated group. In conclusion, our data provided a hint that RGFP966 may be a potential therapeutic medication combating microglia activation and inflammatory response in central nervous system, which was probably related to its repressive impacts on TLR signaling pathways and STAT3/STAT5 pathways.

scholarly journals Role of Toll-like receptor 2 and 4 signaling pathways on the inflammatory response to resistance training in elderly subjects

AGE ◽  
2014 ◽  
Vol 36 (6) ◽  
Author(s):  
Paula Rodriguez-Miguelez ◽  
Rodrigo Fernandez-Gonzalo ◽  
Mar Almar ◽  
Yubisay Mejías ◽  
Ana Rivas ◽  
...  
Keyword(s):  
Resistance Training ◽  
Inflammatory Response ◽  
Signaling Pathways ◽  
Elderly Subjects ◽  
Toll Like Receptor ◽  
Toll Like Receptor 2

scholarly journals Membrane-Associated Proteins of a Lipopolysaccharide-Deficient Mutant of Neisseria meningitidis Activate the Inflammatory Response through Toll-Like Receptor 2

2001 ◽  
Vol 69 (4) ◽  
pp. 2230-2236 ◽  
Author(s):  
Robin R. Ingalls ◽  
Egil Lien ◽  
Douglas T. Golenbock
Keyword(s):  
Cell Wall ◽  
Inflammatory Response ◽  
Neisseria Meningitidis ◽  
Parental Strain ◽  
Host Responses ◽  
Deficient Mutant ◽  
Toll Like Receptor ◽  
Gram Negative ◽  
Negative Cell ◽  
Toll Like Receptor 2

ABSTRACT The recent isolation of a lipopolysaccharide (LPS)-deficient mutant of Neisseria meningitidis has allowed us to explore the roles of other gram-negative cell wall components in the host response to infection. The experiments in this study were designed to examine the ability of this mutant strain to activate cells. Although it was clearly less potent than the parental strain, we found the LPS-deficient mutant to be a capable inducer of the inflammatory response in monocytic cells, inducing a response similar to that seen with Staphylococcus aureus. Cellular activation by the LPS mutant was related to expression of CD14, a high-affinity receptor for LPS and other microbial products, as well as Toll-like receptor 2, a member of the Toll family of receptors recently implicated in host responses to gram-positive bacteria. In contrast to the parental strain, the synthetic LPS antagonist E5564 did not inhibit the LPS-deficient mutant. We conclude that even in the absence of LPS, the gram-negative cell wall remains a potent inflammatory stimulant, utilizing signaling pathways independent of those involved in LPS signaling.

scholarly journals Key Role of CD36 in Toll-Like Receptor 2 Signaling in Cerebral Ischemia

Stroke ◽  
2010 ◽  
Vol 41 (5) ◽  
pp. 898-904 ◽  
Author(s):  
Takato Abe ◽  
Munehisa Shimamura ◽  
Katherine Jackman ◽  
Hitomi Kurinami ◽  
Josef Anrather ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Toll Like Receptor ◽  
Toll Like Receptor 2

Role of toll-like receptor 2 and 4 gene polymorphisms in the development of allergic diseases with increased IgE levels

2012 ◽  
Vol 46 (6) ◽  
pp. 379-383 ◽  
Author(s):  
N. L. Kutsenko ◽  
O. V. Izmailova ◽  
L. E. Vesnina ◽  
I. P. Kaidashev
Keyword(s):  
Gene Polymorphisms ◽  
Allergic Diseases ◽  
Toll Like Receptor ◽  
Toll Like Receptor 2

Role of Toll-like receptor 2 in the immune response against hepadnaviral infection

2012 ◽  
Vol 57 (3) ◽  
pp. 522-528 ◽  
Author(s):  
Xiaoyong Zhang ◽  
Zhiyong Ma ◽  
Hongyan Liu ◽  
Jia Liu ◽  
Zhongji Meng ◽  
...  
Keyword(s):  
Immune Response ◽  
Toll Like Receptor ◽  
Toll Like Receptor 2

1153 – Critical Role of Toll-Like Receptor 2 in Mediating Serotonin Production in Gut

2019 ◽  
Vol 156 (6) ◽  
pp. S-247
Author(s):  
Yun Han Kwon ◽  
Huaqing Wang ◽  
Varun Dewan ◽  
Saad Syed ◽  
Michelle E. Fontes ◽  
...  
Keyword(s):  
Critical Role ◽  
Toll Like Receptor ◽  
Toll Like Receptor 2

scholarly journals Interactions between Yersinia pestis V-antigen (LcrV) and human Toll-like receptor 2 (TLR2) in a modelled protein complex and potential mechanistic insights

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Tiandi Wei ◽  
Jing Gong ◽  
Guojing Qu ◽  
Mingyu Wang ◽  
Hai Xu
Keyword(s):  
Immune Response ◽  
Yersinia Pestis ◽  
Mechanistic Model ◽  
White Blood Cells ◽  
Dynamics Simulation ◽  
Structure Model ◽  
Toll Like Receptor ◽  
Toll Like Receptor 2 ◽  
V Antigen

Abstract Background Yersinia pestis, the etiological pathogen of plague, is capable of repressing the immune response of white blood cells to evade phagocytosis. The V-antigen (LcrV) was found to be involved in this process by binding to human Toll-like Receptor 2 (TLR2). The detailed mechanism behind this LcrV and TLR2 mediated immune response repression, however, is yet to be fully elucidated due to the lack of structural information. Results In this work, with protein structure modelling, we were able to construct a structure model of the heterotetramer of Y. pestis LcrV and human TLR2. Molecular dynamics simulation suggests the stability of this structure in aquatic environment. The LcrV model has a dumbbell-like structure with two globule domains (G1 at N-terminus and G2 away from membrane) connected with a coiled-coil linker (CCL) domain. The two horseshoe-shape TLR2 subunits form a V-shape structure, are not in direct contact with each other, and are held together by the LcrV homodimer. In this structure model, both the G1 and CCL domains are involved in the formation of LcrV homodimer, while all three domains are involved in LcrV-TLR2 binding. A mechanistic model was proposed based on this heterotetrameric structure model: The LcrV homodimer separates the TLR2 subunits to inhibit the dimerization of TLR2 and subsequent signal transfer for immune response; while LcrV could also inhibit the formation of heterodimers of TLR2 with other TLRs, and leads to immune response repression. Conclusions A heterotetrameric structure of Y. pestis LcrV and human TLR2 was modelled in this work. Analysis of this modelled structure showed its stability in aquatic environments and the role of LcrV domains and residues in protein-protein interaction. A mechanistic model for the role of LcrV in Y. pestis pathogenesis is raised based on this heterotetrameric structure model. This work provides a hypothesis of LcrV function, with which further experimental validation may elucidate the role of LcrV in human immune response repression.

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