scholarly journals Involvement of Enteric Glia in Small Intestine Neuromuscular Dysfunction of Toll-Like Receptor 4-Deficient Mice

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 838 ◽  
Author(s):  
Silvia Cerantola ◽  
Valentina Caputi ◽  
Ilaria Marsilio ◽  
Manuela Ridolfi ◽  
Sofia Faggin ◽  
...  
Keyword(s):  
Connexin 43 ◽  
Adenosine Diphosphate ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Neurochemical Coding ◽  
Enteric Glial Cells ◽  
Gfap Immunoreactivity ◽  
Neuromuscular Responses ◽  
Nanc Relaxation ◽  
Mouse Ileum

Enteric glial cells (EGCs) influence nitric oxide (NO)− and adenosine diphosphate (ADP)− mediated signaling in the enteric nervous system (ENS). Since Toll-like receptor 4 (TLR4) participates to EGC homoeostasis, this study aimed to evaluate the possible involvement of EGCs in the alterations of the inhibitory neurotransmission in TLR4−/− mice. Ileal segments from male TLR4−/− and wild-type (WT) C57BL/6J mice were incubated with the gliotoxin fluoroacetate (FA). Alterations in ENS morphology and neurochemical coding were investigated by immunohistochemistry whereas neuromuscular responses were determined by recording non-adrenergic non-cholinergic (NANC) relaxations in isometrically suspended isolated ileal preparations. TLR4−/− ileal segments showed increased iNOS immunoreactivity associated with enhanced NANC relaxation, mediated by iNOS-derived NO and sensitive to P2Y1 inhibition. Treatment with FA diminished iNOS immunoreactivity and partially abolished NO− and ADP− mediated relaxation in the TLR4−/− mouse ileum, with no changes of P2Y1 and connexin-43 immunofluorescence distribution in the ENS. After FA treatment, S100β and GFAP immunoreactivity in TLR4−/− myenteric plexus was reduced to levels comparable to those observed in WT. Our findings show the involvement of EGCs in the alterations of ENS architecture and in the increased purinergic and nitrergic-mediated relaxation, determining gut dysmotility in TLR4−/− mice.

scholarly journals Lipopolysaccharide-Activated Canine Platelets Upregulate High Mobility Group Box-1 via Toll-Like Receptor 4

2021 ◽  
Vol 8 ◽  
Author(s):  
Ronald H. L. Li ◽  
Caelin Hommel ◽  
Nghi Nguyen
Keyword(s):  
Critical Role ◽  
High Mobility ◽  
Adenosine Diphosphate ◽  
Surface Expression ◽  
Multiple Organ ◽  
High Mobility Group ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Hmgb1 Expression ◽  
Granule Secretion

High mobility group box-1 (HMGB1) and the toll-like receptor 4 (TLR4) axis is a key mediator of inflammation. Platelet-derived high mobility group box-1 (HMGB1) may also play a critical role in sepsis-mediated thrombosis resulting in complications like disseminated intravascular coagulation and multiple organ failure. While elevated levels of HMGB1 have been documented in humans and dogs with systemic inflammatory response syndrome and sepsis, a better understanding of how platelet agonists and lipopolysaccharide (LPS) mediate platelet HMGB1 expression would open doors to novel therapies for sepsis-mediated thrombosis. Herein, we sought to determine if canine platelets express HMGB1 in the presence or absence of LPS and agonists (ADP or thrombin) and if surface expression of HMGB1 is dependent on platelet TLR4. Canine platelets were unstimulated (resting) or activated with thrombin or adenosine diphosphate (ADP) in the presence or absence of Escherichia coli LPS prior to flow cytometric and western blot analyses for HMGB1 expression. We also treated canine platelets with or without TLR4 function blocking antibody or its isotype control. We discovered that while thrombin upregulated both surface and cellular HMGB1 expression, LPS-mediated activation in the presence of ADP priming led to upregulation of surface HMGB1 expression. This expression was found to be most prominent in platelets that had undergone alpha-granule secretion. Inhibition of TLR4 attenuated LPS-induced HMGB1 expression indicating that exteriorization of HMGB1 may be dependent on the non-genomic pathway of platelet TLR4. Our findings indicate that upregulation of platelet-derived HMGB1 occurs as a result of thrombin or TLR4-mediated activation in dogs. Future studies should explore the translational implication of platelet-derived HMGB1 as novel therapeutic targets in humans and dogs with sepsis.

660 Deficiency of Toll-like receptor 4 leads to cardioprotection against doxorubicin-induced cardiomyopathy

2007 ◽  
Vol 6 (1) ◽  
pp. 142-143
Author(s):  
A RIAD ◽  
S BIEN ◽  
M GRATZ ◽  
S BERESWILL ◽  
H SCHULTHEISS ◽  
...  
Keyword(s):  
Toll Like Receptor ◽  
Toll Like Receptor 4

Tanshinone IIA attenuates elastase-induced AAA in rats via inhibition of MyD88-dependent TLR-4 signaling

VASA ◽  
2014 ◽  
Vol 43 (1) ◽  
pp. 39-46 ◽  
Author(s):  
Tao Shang ◽  
Feng Ran ◽  
Qian Qiao ◽  
Zhao Liu ◽  
Chang-Jian Liu
Keyword(s):  
Nuclear Factor Κb ◽  
Tanshinone Iia ◽  
Myeloid Differentiation ◽  
Aortic Tissue ◽  
Toll Like Receptor ◽  
Sprague Dawley ◽  
Toll Like Receptor 4 ◽  
Tissue Samples ◽  
Myeloid Differentiation Factor ◽  
And Control

Background: The purpose of this study was to determine whether myeloid differentiation factor88-dependent Toll-Like Receptor-4 (TLR-4) signaling contributed to the inhibition of abdominal aortic aneurysm (AAA) by Tanshinone IIA (Tan IIA). Materials and methods: Male Sprague-Dawley rats (n = 12 / group) were randomly distributed into three groups: Tan IIA, control, and sham. The rats from Tan IIA and control groups under-went intra-aortic elastase perfusion to induce AAAs, and those in the sham group were perfused with saline. Only the Tan IIA group received Tan IIA (2 mg / rat / d). Aortic tissue samples were harvested at 24 d after perfusion and evaluated using reverse transcriptase-polymerase chain reaction, Western blot, immunohistochemistry and immunofluorescence. Results: The over-expression of Toll-Like Receptor-4 (TLR-4), Myeloid Differentiation factor 88 (MyD88), Phosphorylated Nuclear Factor κB (pNF-κB) and Phosphorylated IκBα (pIκBα) induced by elastase perfusion were significantly decreased by Tan IIA treatment. Conclusions: Tan IIA attenuates elastase-induced AAA in rats possibly via the inhibition of MyD88-dependent TLR-4 signaling, which may be one potential explanation of why Tan IIA inhibits AAA development through multiple effects.

Association of the CD14 C159T and the Toll-like receptor 4 Asp299Gly polymorphisms with various phenotypes of asthma in adults from Crimea

2020 ◽  
Vol 41 (2) ◽  
pp. 134-140
Author(s):  
Yuriy Bisyuk ◽  
Andrew Dubovyi ◽  
Ilona DuBuske ◽  
Viktor Litus ◽  
Lawrence M. DuBuske
Keyword(s):  
Late Onset ◽  
Adult Population ◽  
Additive Models ◽  
Atopic Asthma ◽  
Control Group ◽  
Nucleotide Polymorphisms ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Single Nucleotide ◽  
Gender And Age

Background: This study assessed gene polymorphisms of the CD14 receptor (C-159T) and Toll-like receptor 4 (Asp299Gly) in a patient population in Crimea, Ukraine, stratified by clinical (early versus late onset; frequent versus occasional relapses; fixed versus reversible obstruction) and immunologic (atopic versus nonatopic; eosinophilic; neutrophilic or paucigranulocytic inflammation) subtype. Methods: Two polymorphisms, CD14 C-159T and TLR4 Asp299Gly, were assessed in 331 patients with asthma. The control group included 285 volunteers who were nonatopic. The single nucleotide polymorphisms were studied by using polymerase chain reaction with electrophoretic detection. Results: There were increased odds of asthma development in patients with the Asp299Gly TLR4 mutation compared with the general population underdominant odds ratio (OR) 1.52 [95% confidence interval (CI), 1.00‐2.32] and overdominant (OR 1.55 [95% CI, 1.01‐2.38]) models after adjustment for gender and age. In addition, mutations in this gene decreased the odds of nonatopic asthma in underdominant (OR 0.26 [95% CI, 0.07‐0.93]; p = 0.027), overdominant (OR 0.27 [95% CI, 0.07‐0.96]; p = 0.033), and log-additive models (OR 0.26 [95% CI, 0.07‐0.93]; p = 0.026) compared with the atopic subgroup after adjustment for gender, age, number of exacerbations, and type of airway inflammation. Allele frequencies for CD14 and TLR4 polymorphisms did not show statistical differences between the patients with asthma and the control subjects. Conclusion: CD14 C-159T polymorphisms were not associated with asthma in the adult population in Crimea. TLR4 Asp299Gly polymorphisms were associated with asthma and with decreased odds of nonatopic asthma compared with atopic asthma in the adult population in Crimea.

Sign in / Sign up

Export Citation Format

Share Document