scholarly journals Whey Acidic Protein/Four-Disulfide Core Domain 21 Regulate Sepsis Pathogenesis in a Mouse Model and a Macrophage Cell Line via the Stat3/Toll-Like Receptor 4 (TLR4) Signaling Pathway

2018 ◽  
Vol 24 ◽  
pp. 4054-4063 ◽  
Author(s):  
Zhixiang Xie ◽  
Zhuangbo Guo ◽  
Jianfeng Liu
Keyword(s):  
Mouse Model ◽  
Cell Line ◽  
Signaling Pathway ◽  
Toll Like Receptor ◽  
Macrophage Cell Line ◽  
Macrophage Cell ◽  
Toll Like Receptor 4 ◽  
Tlr4 Signaling ◽  
Core Domain ◽  
Tlr4 Signaling Pathway

scholarly journals Toll-Like Receptor 4 (TLR4)-Deficient Murine Macrophage Cell Line as an In Vitro Assay System To Show TLR4-Independent Signaling of Bacteroides fragilis Lipopolysaccharide

2002 ◽  
Vol 70 (9) ◽  
pp. 4892-4896 ◽  
Author(s):  
Eva Lorenz ◽  
Dhavalkumar D. Patel ◽  
Thomas Hartung ◽  
David A. Schwartz
Keyword(s):  
Cell Line ◽  
Mouse Strain ◽  
Bacterial Species ◽  
Bacteroides Fragilis ◽  
Toll Like Receptor ◽  
Macrophage Cell Line ◽  
Macrophage Cell ◽  
Toll Like Receptor 4 ◽  
Necrosis Factor Alpha ◽  
Vitro Assay

ABSTRACT Bacterial lipopolysaccharides (LPS) activate cells of innate immunity, such as macrophages, by stimulating signaling through toll-like receptor 4 (TLR4). We and others have hypothesized that LPS derived from different bacterial species may function through TLR4-independent mechanisms. To test this hypothesis, we have generated using a nonviral transformation procedure a bone marrow-derived macrophage cell line called 10ScNCr/23 from mouse strain C57BL/10ScNCr. This mouse strain has a deletion of the TLR4 locus, causing the mouse strain to be nonresponsive to stimulation by LPS from Escherichia coli while responding normally to other bacterial substrates, such as lipoteichoic acid (LTA) from Staphylococcus aureus, which signal TLR4 independently. Stimulation with LTA induces five- and sixfold increases in 10ScNCr/23 cell line tumor necrosis factor alpha and macrophage inflammatory protein-2 (MIP-2) secretion, but no increases in either cytokine were found when cells were stimulated with E. coli LPS. Bacteroides fragilis-derived LPS, however, can effectively stimulate MIP-2 expression in the absence of functional TLR4 in the 10ScNCr/23 cell line. This gives rise to the notion that LPS from some bacterial species will utilize alternative receptors to stimulate the innate immune response.

scholarly journals Dietary Silk Peptide Inhibits LPS-Induced Inflammatory Responses by Modulating Toll-Like Receptor 4 (TLR4) Signaling

Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 771
Author(s):  
Sungwoo Chei ◽  
Hyun-Ji Oh ◽  
Kippeum Lee ◽  
Heegu Jin ◽  
Jeong-Yong Lee ◽  
...  
Keyword(s):  
Immune Responses ◽  
Signaling Pathway ◽  
Inflammatory Responses ◽  
Innate Immune Responses ◽  
Toll Like Receptor ◽  
Serum Samples ◽  
Toll Like Receptor 4 ◽  
Tlr4 Signaling ◽  
Tlr4 Signaling Pathway ◽  
Silk Peptide

Acid-hydrolyzed silk peptide (SP) is a valuable material that has been used traditionally to treat various diseases, however, the mechanism by which it affects inflammatory responses is unknown. To examine the effects of SP on inflammatory responses, we used macrophages as a vehicle for examining signaling via toll-like receptor 4 (TLR4), which plays an important role in innate immune responses to pathogenic infections and pathogen-derived molecules such as lipopolysaccharide (LPS). We then confirmed the anti-inflammatory effects of SP by examining lymph node, spleen, and serum samples from C57BL/6 mice injected with LPS. We also used LPS-induced bone marrow-derived macrophages and RAW264.7 cells (a murine macrophage cell line) to identify the mechanism by which SP modulates immune responses via the TLR4 signaling pathway. In addition, we showed that SP prevents LPS-induced production of nitric oxide and reactive oxygen species. In summary, SP inhibits LPS-induced inflammatory responses by modulating the TLR4 signaling pathway.

scholarly journals Dahuang Zexie Decoction Protects against High-Fat Diet-Induced NAFLD by Modulating Gut Microbiota-Mediated Toll-Like Receptor 4 Signaling Activation and Loss of Intestinal Barrier

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Jing Fang ◽  
Xiaoqi Sun ◽  
Boyu Xue ◽  
Nanyuan Fang ◽  
Min Zhou
Keyword(s):  
Gut Microbiota ◽  
Signaling Pathway ◽  
High Fat Diet ◽  
Intestinal Barrier ◽  
Toll Like Receptor ◽  
High Fat ◽  
Toll Like Receptor 4 ◽  
Tlr4 Signaling ◽  
Tlr4 Signaling Pathway ◽  
Signaling Activation

Increasing evidence suggests that intestinal dysbiosis, intestinal barrier dysfunction, and activated Toll-like receptor 4 (TLR4) signaling play key roles in the pathogenesis of NAFLD. Dahuang Zexie Decoction (DZD) has been verified to be effective for treating NAFLD, but the mechanisms remain unclear. In this study, we investigated the effects of DZD on NAFLD rats and determined whether such effects were associated with change of the gut microbiota, downregulated activity of the TLR4 signaling pathway, and increased expressions of tight junction (TJ) proteins in the gut. Male Sprague Dawley rats were fed high-fat diet (HFD) for 16 weeks to induce NAFLD and then given DZD intervention for 4 weeks. We found that DZD reduced body and liver weights of NAFLD rats, improved serum lipid levels and liver function parameters, and relieved NAFLD. We further found that DZD changed intestinal bacterial communities, inhibited the intestinal TLR4 signaling pathway, and restored the expressions of TJ proteins in the gut. Meanwhile ten potential components of DZD had been identified. These findings suggest that DZD may protects against NAFLD by modulating gut microbiota-mediated TLR4 signaling activation and loss of intestinal barrier. However, further studies are needed to clarify the mechanism by which DZD treats NAFLD.

Neuroprotection of chicoric acid in a mouse model of Parkinson's disease involves gut microbiota and TLR4 signaling pathway

2022 ◽  
Author(s):  
Ning Wang ◽  
Bainian Feng ◽  
Bin Hu ◽  
Yuliang Cheng ◽  
Yahui Guo ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Gut Microbiota ◽  
Signaling Pathway ◽  
Echinacea Purpurea ◽  
Tlr4 Signaling ◽  
Chicoric Acid ◽  
Purple Coneflower ◽  
Tlr4 Signaling Pathway

Chicoric acid (CA), a polyphenolic acid obtained from chicory and purple coneflower (Echinacea purpurea), has been regarded as nutraceutical to combat inflammation, virus and obesity. Parkinson’s Disease (PD) is a...

scholarly journals Effects of Chronic Mild Stress on the Development of Atherosclerosis and Expression of Toll-Like Receptor 4 Signaling Pathway in Adolescent Apolipoprotein E Knockout Mice

2009 ◽  
Vol 2009 ◽  
pp. 1-13 ◽  
Author(s):  
Hongfeng Gu ◽  
Chaoke Tang ◽  
Kuang Peng ◽  
Hui Sun ◽  
Yongzong Yang
Keyword(s):  
Apolipoprotein E ◽  
Signaling Pathway ◽  
Knockout Mice ◽  
Chronic Mild Stress ◽  
Mild Stress ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Apolipoprotein E Knockout Mice ◽  
Tlr4 Signaling Pathway ◽  
Myeloid Differentiation Factor

Here, we investigated the effect of chronic mild stress (CMS) on the development of atherosclerosis as well as the expression of Toll-like receptors (TLRs) signaling pathway in adolescent apolipoprotein E knockout (apoE-/-) mice. Mice were subjected to daily CMS for 0, 4, and 12 weeks, respectively. To identify the expression of Toll-like receptor 4 signaling pathway in adolescent apolipoprotein E knockout mice subjected to CMS, we compared gene expression in aortas of stressed and unstressed mice using TLRs signaling pathway real-time PCR microarrays consisting of 87 genes. We found that atherosclerosis lesions both in aortic tress and sinuses of CMS mice were significantly increased linearly in response to duration of CMS exposure. Among 87 genes analyzed, 15 genes were upregulated in stressed mice, especially TLR4, myeloid differentiation factor 88 (MyD88), and IL-1β, and 28 genes were downregulated compared with nonstressed mice. CMS mice demonstrated markedly increased aortic atherosclerosis that were associated with significant increases in levels of expression of TLR4, MyD88, nuclear factorκB (NF-κB), MCP-1, IL-1β, TNF-α, and sICAM-1. Taken together, our results suggest an important role for TLR4 signaling pathway in atherosclerosis in a CMS mouse model.

scholarly journals Fecal microbiota transplantation protects rotenone-induced Parkinson’s disease mice via suppressing inflammation mediated by the lipopolysaccharide-TLR4 signaling pathway through the microbiota-gut-brain axis

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Zhe Zhao ◽  
Jingwen Ning ◽  
Xiu-qi Bao ◽  
Meiyu Shang ◽  
Jingwei Ma ◽  
...  
Keyword(s):  
Mouse Model ◽  
Gut Microbiota ◽  
Signaling Pathway ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Motor Deficits ◽  
Tlr4 Signaling ◽  
Tlr4 Signaling Pathway ◽  
The Brain ◽  
Gut Microbiota Dysbiosis

Abstract Background Parkinson’s disease (PD) is a prevalent neurodegenerative disorder, displaying not only well-known motor deficits but also gastrointestinal dysfunctions. Consistently, it has been increasingly evident that gut microbiota affects the communication between the gut and the brain in PD pathogenesis, known as the microbiota-gut-brain axis. As an approach to re-establishing a normal microbiota community, fecal microbiota transplantation (FMT) has exerted beneficial effects on PD in recent studies. Here, in this study, we established a chronic rotenone-induced PD mouse model to evaluate the protective effects of FMT treatment on PD and to explore the underlying mechanisms, which also proves the involvement of gut microbiota dysbiosis in PD pathogenesis via the microbiota-gut-brain axis. Results We demonstrated that gut microbiota dysbiosis induced by rotenone administration caused gastrointestinal function impairment and poor behavioral performances in the PD mice. Moreover, 16S RNA sequencing identified the increase of bacterial genera Akkermansia and Desulfovibrio in fecal samples of rotenone-induced mice. By contrast, FMT treatment remarkably restored the gut microbial community, thus ameliorating the gastrointestinal dysfunctions and the motor deficits of the PD mice. Further experiments revealed that FMT administration alleviated intestinal inflammation and barrier destruction, thus reducing the levels of systemic inflammation. Subsequently, FMT treatment attenuated blood-brain barrier (BBB) impairment and suppressed neuroinflammation in the substantia nigra (SN), which further decreased the damage of dopaminergic neurons. Additional mechanistic investigation discovered that FMT treatment reduced lipopolysaccharide (LPS) levels in the colon, the serum, and the SN, thereafter suppressing the TLR4/MyD88/NF-κB signaling pathway and its downstream pro-inflammatory products both in the SN and the colon. Conclusions Our current study demonstrates that FMT treatment can correct the gut microbiota dysbiosis and ameliorate the rotenone-induced PD mouse model, in which suppression of the inflammation mediated by the LPS-TLR4 signaling pathway both in the gut and the brain possibly plays a significant role. Further, we prove that rotenone-induced microbiota dysbiosis is involved in the genesis of PD via the microbiota-gut-brain axis.

scholarly journals Chicken avian β-defensin 8 modulates immune response via the mitogen-activated protein kinase signaling pathways in a chicken macrophage cell line

2020 ◽  
Author(s):  
Yeojin Hong ◽  
Thu Thao Pham ◽  
Jiae Lee ◽  
Hyun S. Lillehoj ◽  
Yeong Ho Hong
Keyword(s):  
Protein Kinase ◽  
Cell Line ◽  
Signaling Pathway ◽  
Proinflammatory Cytokines ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Macrophage Cell Line ◽  
Macrophage Cell ◽  
Mitogen Activated Protein ◽  
Chicken Macrophage

Abstract Background: Defensins are antimicrobial peptides composed of three conserved disulfide bridges, a β-sheet, and both hydrophobic and cationic amino acids. In this study, we aimed to demonstrate the immunomodulation role of avian β-defensin 8 (AvBD8) in a chicken macrophage cell line. Results: Chicken AvBD8 stimulated the expression of proinflammatory cytokines (interleukin (IL)-1β, interferon-γ, and IL-12p40) and chemokines (CCL4, CXCL13, and CCL20) in macrophages. Furthermore, by western blotting and immunocytochemistry, we confirmed that AvBD8 activated the mitogen-activated protein kinase (MAPK) signaling pathway via extracellular regulated kinases 1/2 (ERK1/2) and p38 signaling molecules. Conclusion: Overall, AvBD8 regulates host immune system as not only an antimicrobial peptide, but also an immunomodulator by activating the MAPK signaling pathway and inducing the expression of proinflammatory cytokines and chemokines.

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