Study The Effects Of Systemic Injection Of Escherichia coli Lipopolysaccharide  On The Expression Profile Of TLR4 And CD14 Genes Of Rats Liver

Al-AAlim, Ammar M.; Aliedani, Ali; Hamad, Mohammad A.

doi:10.5455/ovj.2021.v11.i4.30

Cited by 6 publications

(2 citation statements)

References 23 publications

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“…This is unexpected, given that B cells from healthy humans generally do not express TLR4 and do not respond to LPS stimulation [ 43 , 44 ]. In previous studies, short-term high dose of LPS stimulation may result in TLR4 downregulation in cells in vitro [ 45 – 47 ] but conflict results were also reported [ 48 , 49 ]. Nonetheless, the effect of long-term low dose of LPS repeated stimulation on TLR4 remains unknown.…”

Section: Discussionmentioning

confidence: 97%

Impacts of plasma microbial lipopolysaccharide translocation on B cell perturbations and anti-CD4 autoantibody production in people with HIV on suppressive antiretroviral therapy

Cheng

Luo

et al. 2023

Cell Biosci

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Background . Up to 20% of people with HIV (PWH) who undergo virologically suppressed antiretroviral therapy (ART) fail to experience complete immune restoration. We recently reported that plasma anti-CD4 IgG (antiCD4IgG) autoantibodies from immune non-responders specifically deplete CD4 + T cells via antibody-dependent cytotoxicity. However, the mechanism of antiCD4IgG production remains unclear. Methods . Blood samples were collected from 16 healthy individuals and 25 PWH on suppressive ART. IgG subclass, plasma lipopolysaccharide (LPS), and antiCD4IgG levels were measured by ELISA. Gene profiles in B cells were analyzed by microarray and quantitative PCR. Furthermore, a patient-derived antiCD4IgG–producing B cell line was generated and stimulated with LPS in vitro. B cell IgG class switch recombination (CSR) was evaluated in response to LPS in splenic B cells from C57/B6 mice in vitro. Results . Increased plasma anti-CD4 IgGs in PWH were predominantly IgG1 and associated with increased plasma LPS levels as well as B cell expression of TLR2, TLR4, and MyD88 mRNA in vivo. Furthermore, LPS stimulation induced antiCD4IgG production in the antiCD4IgG B cell line in vitro. Finally, LPS promoted CSR in vitro. Conclusion . Our findings suggest that persistent LPS translocation may promote anti-CD4 autoreactive B cell activation and antiCD4IgG production in PWH on ART, which may contribute to gradual CD4 + T cell depletion. This study suggests that reversing a compromised mucosal barrier could improve ART outcomes in PWH who fail to experience complete immune restoration.

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Section: Discussionmentioning

confidence: 97%

Impacts of plasma microbial lipopolysaccharide translocation on B cell perturbations and anti-CD4 autoantibody production in people with HIV on suppressive antiretroviral therapy

Cheng

Luo

et al. 2023

Cell Biosci

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“…Endotoxin is sensed by human cells as a pathogen-associated molecular pattern. It is able both activate membrane-bound TLR4 and CD14 receptors (Mazgaeen & Gurung, 2020) and stimulate their gene expression in phagocytic cells (Al-Aalim et al, 2021), thus inducing NF-κB and inflammatory cytokine production. Some cytoplasmic sensors are involved in the recognition of endotoxin that has entered the cell (Mazgaeen & Gurung, 2020).…”

Section: Bacterial Endotoxinmentioning

confidence: 99%

Endogenous humoral determinants of vascular endothelial dysfunction as triggers of acute poisoning complications

Ivnitsky

Schäfer²,

Rejniuk

et al. 2022

J of Applied Toxicology

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The vascular endothelium is not only the semipermeable membrane that separates tissue from blood but also an organ that regulates inflammation, vascular tone, blood clotting, angiogenesis and synthesis of connective tissue proteins. It is susceptible to the direct cytotoxic action of numerous xenobiotics and to the acute hypoxia that accompanies acute poisoning. This damage is superimposed on the preformed state of the vascular endothelium, which, in turn, depends on many humoral factors. The probability that an exogenous toxicant will cause lifethreatening dysfunction of the vascular endothelium, thereby complicating the course of acute poisoning, increases with an increase in the content of endogenous substances in the blood that disrupt endothelial function. These include ammonia, bacterial endotoxin, indoxyl sulfate, para-cresyl sulfate, trimethylamine N-oxide, asymmetric dimethylarginine, glucose, homocysteine, low-density and very-lowdensity lipoproteins, free fatty acids and products of intravascular haemolysis. Some other endogenous substances (albumin, haptoglobin, haemopexin, biliverdin, bilirubin, tetrahydrobiopterin) or food-derived compounds (ascorbic acid, rutin, omega-3 polyunsaturated fatty acids, etc.) reduce the risk of lethal vascular endothelial dysfunction. The individual variability of the content of these substances in the blood contributes to the stochasticity of the complications of acute poisoning and is a promising target for the risk reduction measures. Another feasible option may be the repositioning of drugs that affect the function of the vascular endothelium while being currently used for other indications.

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Knocking out Fkbp51 decreases CCl4-induced liver injury through enhancement of mitochondrial function and Parkin activity

Qiu,

Zhong,

Dou

et al. 2024

Cell Biosci

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Background and aims Previously, we found that FK506 binding protein 51 (Fkbp51) knockout (KO) mice resist high fat diet-induced fatty liver and alcohol-induced liver injury. The aim of this research is to identify the mechanism of Fkbp51 in liver injury. Methods Carbon tetrachloride (CCl4)-induced liver injury was compared between Fkbp51 KO and wild type (WT) mice. Step-wise and in-depth analyses were applied, including liver histology, biochemistry, RNA-Seq, mitochondrial respiration, electron microscopy, and molecular assessments. The selective FKBP51 inhibitor (SAFit2) was tested as a potential treatment to ameliorate liver injury. Results Fkbp51 knockout mice exhibited protection against liver injury, as evidenced by liver histology, reduced fibrosis-associated markers and lower serum liver enzyme levels. RNA-seq identified differentially expressed genes and involved pathways, such as fibrogenesis, inflammation, mitochondria, and oxidative metabolism pathways and predicted the interaction of FKBP51, Parkin, and HSP90. Cellular studies supported co-localization of Parkin and FKBP51 in the mitochondrial network, and Parkin was shown to be expressed higher in the liver of KO mice at baseline and after liver injury relative to WT. Further functional analysis identified that KO mice exhibited increased ATP production and enhanced mitochondrial respiration. KO mice have increased mitochondrial size, increased autophagy/mitophagy and mitochondrial-derived vesicles (MDV), and reduced reactive oxygen species (ROS) production, which supports enhancement of mitochondrial quality control (MQC). Application of SAFit2, an FKBP51 inhibitor, reduced the effects of CCl4-induced liver injury and was associated with increased Parkin, pAKT, and ATP production. Conclusions Downregulation of FKBP51 represents a promising therapeutic target for liver disease treatment. Graphical Abstract

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Study The Effects Of Systemic Injection Of Escherichia coli Lipopolysaccharide On The Expression Profile Of TLR4 And CD14 Genes Of Rats Liver

Cited by 6 publications

References 23 publications

Impacts of plasma microbial lipopolysaccharide translocation on B cell perturbations and anti-CD4 autoantibody production in people with HIV on suppressive antiretroviral therapy

Impacts of plasma microbial lipopolysaccharide translocation on B cell perturbations and anti-CD4 autoantibody production in people with HIV on suppressive antiretroviral therapy

Endogenous humoral determinants of vascular endothelial dysfunction as triggers of acute poisoning complications

Knocking out Fkbp51 decreases CCl4-induced liver injury through enhancement of mitochondrial function and Parkin activity

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