scholarly journals The Absence of TLR4 Prevents Fetal Brain Injury in the Setting of Intrauterine Inflammation

2018 ◽  
Vol 26 (8) ◽  
pp. 1082-1093 ◽  
Author(s):  
Natalia M. Tulina ◽  
Amy G. Brown ◽  
Guillermo O. Barila ◽  
Michal A. Elovitz
Keyword(s):  
Brain Injury ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Quantitative Polymerase Chain Reaction ◽  
Fetal Brain ◽  
Notch Signaling Pathway ◽  
Mouse Strains ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tlr4 Signaling ◽  
Tlr4 Signaling Pathway

Background: Exposure to intrauterine inflammation during pregnancy is linked to brain injury and neurobehavioral disorders in affected children. Innate immunity, specifically Toll-like receptor (TLR) signaling pathways are present throughout the reproductive tract as well as in the placenta, fetal membranes, and fetus. The TLR pathways are mechanistically involved in host responses to foreign pathogens and may lead to brain injury associated with prenatal inflammation. Objective: We aimed to determine whether the activation of the TLR4 signaling pathway, in the mother and fetus, is critical to fetal brain injury in the setting of intrauterine inflammation. Methods: A mini-laparotomy was performed on time pregnant C57B6 mice and 2 knockout mouse strains lacking the function of the Tlr4 and Myd88 genes on embryonic day 15. Intrauterine injections of Escherichia coli lipopolysaccharide or saline were administered as described previously. Dams were killed 6 hours postsurgery, and placental, amniotic fluid, and fetal brain tissue were collected. To assess brain injury, quantitative polymerase chain reaction (qPCR) analysis was performed on multiple components of the NOTCH signaling pathway, including Hes genes. Interleukin (IL) IL6, IL1β, and CCL5 expression was assessed using qPCR and enzyme-linked immunosorbent assay. Results: Using an established mouse model of intrauterine inflammation, we demonstrate that the abrogation of TLR4 signaling eliminates the cytokine response in mother and fetus and prevents brain injury associated with increased expression of transcriptional effectors of the NOTCH signaling pathway, Hes1 and Hes5. Conclusions: These data show that the activation of the TLR4 signaling pathway is necessary for the development of fetal brain injury in response to intrauterine inflammation.

scholarly journals Electroacupuncture Improved Hippocampal Neurogenesis following Traumatic Brain Injury in Mice through Inhibition of TLR4 Signaling Pathway

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Yuqin Ye ◽  
Yongxiang Yang ◽  
Chen Chen ◽  
Ze Li ◽  
Yanfeng Jia ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Signaling Pathway ◽  
Neurological Diseases ◽  
Inhibitory Effect ◽  
Protective Role ◽  
Hippocampal Neurogenesis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tlr4 Signaling ◽  
Tlr4 Signaling Pathway

The protective role of electroacupuncture (EA) treatment in diverse neurological diseases such as ischemic stroke is well acknowledged. However, whether and how EA act on hippocampal neurogenesis following traumatic brain injury (TBI) remains poorly understood. This study aims to investigate the effect of EA on hippocampal neurogenesis and neurological functions, as well as its underlying association with toll-like receptor 4 (TLR4) signaling in TBI mice. BrdU/NeuN immunofluorescence was performed to label newborn neurons in the hippocampus after EA treatment. Water maze test and neurological severity score were used to evaluate neurological function posttrauma. The hippocampal level of TLR4 and downstream molecules and inflammatory cytokines were, respectively, detected by Western blot and enzyme-linked immunosorbent assay. EA enhanced hippocampal neurogenesis and inhibited TLR4 expression at 21, 28, and 35 days after TBI, but the beneficial effects of EA on posttraumatic neurogenesis and neurological functions were attenuated by lipopolysaccharide-induced TLR4 activation. In addition, EA exerted an inhibitory effect on both TLR4/Myd88/NF-κB and TLR4/TRIF/NF-κB pathways, as well as the inflammatory cytokine expression in the hippocampus following TBI. In conclusion, EA promoted hippocampal neurogenesis and neurological recovery through inhibition of TLR4 signaling pathway posttrauma, which may be a potential approach to improve the outcome of TBI.

Effects of Cornu Bubali (CB) on the Adhesion of Leukocyte and Endothelial Cells

2020 ◽  
Vol 10 (4) ◽  
pp. 554-561
Author(s):  
Haixia Li ◽  
Zhenghui Xiao ◽  
Xuefei Tian ◽  
Paoqiu Wang ◽  
Yan Long ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Western Blot ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Umbilical Vein ◽  
Quantitative Polymerase Chain Reaction ◽  
Notch Signaling Pathway ◽  
Dependent Manner ◽  
Qpcr Analysis ◽  
Tnf Α

Background: The interaction between leukocytes and vascular endothelial cells is ubiquitous in the occurrence and development of many diseases, especially in the body's defense response. The purpose of the present study was to investigate the effect of cornu bubali (CB) on the adhesion of leukocytes to endothelial cells. Materials and methods: Human leukemic cell line (HL-60) and human umbilical vein endothelial cells (HUVECs) were used to simulate the adhesion effect between cells. After HUVECs were treated with TNF- α(15 ng/mL) combined with different dose of CB (15, 30 and 60 μmol/L) and dexamethasone (DEX, 2 μg/ml) for 24 h, HL-60 cells were added into the coculture system for another 1 h. CCK8 assay was performed to investigate cell viability of HUVECs. HL-60 cells adhesion to HUVECs was quantified using Hoechst 33342 staining. Subsequently, the levels of adhesion molecules were detected by the reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis and ELISA, respectively. RT-qPCR and western blot were performed to assess the levels of inflammatory cytokines, chemokines and the expression of Notch signaling pathway. Results: Treatment with CB could reduce the adherence of HL-60 to HUVECs induced by TNF- in a dose-dependent manner. CB inhibited the expression of ICAM-1, VCAM-1, CD44, IL-1β, COX-2 and CCL4 in HUVECs. Western blot and RT-qPCR analysis confirmed that CB prevented TNF-α -induced over-expression of Notch receptors (Notch1 and Notch2), Notch ligands (DLL1 and Jagged1), signaling effectors (Hes1) and adhesion related proteins (NF-κB/p65, p-I B and IκBκ) in HUVECs. Conclusion: CB induces interactions between leukocytes and endothelial cells through the activation of Notch signaling pathway. These data contribute to further explain the protective effect of CB against development of inflammatory process of hemorrhage in acute leukemia.

scholarly journals Glycyrrhizin Ameliorates Radiation Enteritis in Mice Accompanied by the Regulation of the HMGB1/TLR4 Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Xiao-min Zhang ◽  
Xiao Hu ◽  
Jin-ying Ou ◽  
Shan-shan Chen ◽  
Ling-hui Nie ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Inflammatory Cytokines ◽  
Molecular Mechanisms ◽  
Radiation Enteritis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Intestinal Damage ◽  
Tlr4 Signaling ◽  
Pelvic Malignancies ◽  
Tlr4 Signaling Pathway ◽  
Anti Inflammatory

Radiation enteritis is a common side effect of radiotherapy for abdominal and pelvic malignancies, which can lead to a decrease in patients’ tolerance to radiotherapy and the quality of life. It has been demonstrated that glycyrrhizin (GL) possesses significant anti-inflammatory activity. However, little is known about its anti-inflammatory effect in radiation enteritis. In the present study, we aimed to investigate the potential anti-inflammatory effects of GL on radiation enteritis and elucidate the possible underlying molecular mechanisms involved. The C57BL/6 mice were subjected to 6.5 Gy abdominal X-ray irradiation to establish a model of radiation enteritis. Hematoxylin and eosin staining was performed to analyze the pathological changes in the jejunum. The expression of TNF-α in the jejunum was analyzed by immunochemistry. The levels of inflammatory cytokines, such as TNF-α, IL-6, IL-1β, and HMGB1 in the serum were determined by enzyme-linked immunosorbent assay. The intestinal absorption capacity was tested using the D-xylose absorption assay. The levels of HMGB1 and TLR4 were analyzed by western blotting and immunofluorescence staining. We found that GL significantly alleviated the intestinal damage and reduced the levels of inflammatory cytokines, such as TNF-α, IL-6, IL-1β, and HMGB1 levels. Furthermore, the HMGB1/TLR4 signaling pathway was significantly downregulated by GL treatment. In conclusion, these findings indicate that GL has a protective effect against radiation enteritis through the inhibition of the intestinal damage and the inflammatory responses, as well as the HMGB1/TLR4 signaling pathway. Thereby, GL might be a potential therapeutic agent for the treatment of radiation enteritis.

MiR-200c-3p increased HDMEC proliferation through the notch signaling pathway

2021 ◽  
pp. 153537022098185
Author(s):  
Xianyu Hu ◽  
Suwen Bai ◽  
Lingyi Li ◽  
Pengfei Tian ◽  
Sun Wang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Vascular Endothelial Cells ◽  
Notch Signaling Pathway ◽  
Healthy Tissue ◽  
Cell Counting ◽  
Enzyme Linked Immunosorbent Assay ◽  
Vascular Endothelial ◽  
Bioinformatics Analyses

Excessive proliferation of vascular endothelial cells can cause hemangioma. Although typically benign, hemangiomas can become life-threatening. The microRNA miR-200c-3p is abnormally expressed in some types of tumors, but its expression, biological role, and mechanism of action in infantile hemangioma remain to be fully elucidated. The expression levels of miR-200c-3p in hemangioma tissue were compared with those in adjacent healthy tissue by using bioinformatics analyses and TargetScan. Western blot, enzyme-linked immunosorbent assay, and Cell Counting Kit 8 analyses were used to determine the biological function and site of action of miR-200c-3p in human dermal microvascular endothelial cells (HDMECs). MiR-200c-3p was one of the top 10 differentially expressed genes between healthy tissue, and hemangiomas tissues, having markedly decreased expression in hemangioma tissue. Reduction of miR-200c-3p expression in HDMECs through the transfection of a miR-200c-3p inhibitor significantly increased HDMEC proliferation. The addition of the Notch signaling pathway inhibitor DAPT to HDMECs transfected with the miR-200c-3p inhibitor eliminated the inhibitor-induced enhancement of proliferation in HDMECs. These findings indicate that miR-200c-3p targets the Notch signaling pathway to promote the proliferation of vascular endothelial cells, suggesting that miR-200c-3p plays an important role in the pathogenesis of hemangioma.

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