scholarly journals SP398CRUCIAL ROLE OF ARYL HYDROCARBON RECEPTOR IN INDOXYL Sulfate-INDUCED VASCULAR INFLAMMATION

2015 ◽  
Vol 30 (suppl_3) ◽  
pp. iii510-iii511
Author(s):  
Shunsuke Ito ◽  
Mizuko Osaka ◽  
Naoki Sawada ◽  
Takeo Edamatsu ◽  
Yoshiharu Itoh ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Vascular Inflammation ◽  
Indoxyl Sulfate ◽  
Aryl Hydrocarbon

scholarly journals Crucial Role of the Aryl Hydrocarbon Receptor (AhR) in Indoxyl Sulfate-Induced Vascular Inflammation

2016 ◽  
Vol 23 (8) ◽  
pp. 960-975 ◽  
Author(s):  
Shunsuke Ito ◽  
Mizuko Osaka ◽  
Takeo Edamatsu ◽  
Yoshiharu Itoh ◽  
Masayuki Yoshida
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Crucial Role ◽  
Vascular Inflammation ◽  
Indoxyl Sulfate ◽  
Aryl Hydrocarbon

scholarly journals Role of Resveratrol on Indoxyl Sulfate-Induced Endothelial Hyperpermeability via Aryl Hydrocarbon Receptor (AHR)/Src-Dependent Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Eskedar Getachew Assefa ◽  
Qiaoqiao Yan ◽  
Siameregn Berhe Gezahegn ◽  
Maibouge Tanko Mahamane Salissou ◽  
Shuiqing He ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Src Kinase ◽  
Endothelial Permeability ◽  
High Serum ◽  
Indoxyl Sulfate ◽  
Dietary Polyphenols ◽  
Aryl Hydrocarbon ◽  
Dependent Pathway ◽  
Endothelial Hyperpermeability

Resveratrol (RES), a dietary polyphenol compound, has been shown to possess health benefits due to its anti-inflammatory, antioxidative, and antiatherosclerosis properties. Tryptophan metabolite-derived indoxyl sulfate (IS) is identified as one of the uremic toxins and physiological endogenous ligand/activator of aryl hydrocarbon receptor (AHR), associated with atherosclerosis in chronic kidney disease (CKD) patients. Studies have shown that a high serum level of IS causes deleterious effects on health primarily by inducing oxidative stress and endothelial dysfunction. However, the precise mechanisms are still unclear. Here, we investigated the underlying mechanism of IS effect on endothelial permeability and the role of RES on IS-induced endothelial hyperpermeability via the AHR/Src-dependent pathway. Bovine aorta endothelial cells (BAECs) were cultured and incubated with IS in the presence or absence of RES, and transendothelial electrical resistance (TEER) and permeability of cells were measured. Alongside, AHR, Src kinase, and Vascular Endothelial Cadherin (VE-Cadherin) activation were examined. Our data showed that IS reduced TEER of cells resulting in increased permeability. VE-Cadherin, a vital regulator of endothelial permeability, was also significantly activated in response to IS, which appeared to be associated with changes of endothelial permeability and AHR/Src kinase. Interestingly, in this setting, RES reversed the effect of IS and inhibited the increased activation of Src induced by IS-activated AHR and modulated VE-Cadherin and permeability. CH223191, an inhibitor of AHR, significantly inhibits IS-induced endothelial hyperpermeability. Further analysis with treatment of PP2, an inhibitor of Src abolishing Src activation, suggests downstream factors. All our data indicated that IS upregulated the AHR/Src kinase pathway, and increased endothelial permeability and phosphorylation of VE-Cadherin may be represented and provide new strategies for addressing protective properties of RES against Src kinase involved in AHR-mediated endothelial hyperpermeability. The findings may be crucial for managing diseases in which endothelial permeability is compromised, and the dietary polyphenols are involved.

scholarly journals Concentration and Duration of Indoxyl Sulfate Exposure Affects Osteoclastogenesis by Regulating NFATc1 via Aryl Hydrocarbon Receptor

2020 ◽  
Vol 21 (10) ◽  
pp. 3486 ◽  
Author(s):  
Wen-Chih Liu ◽  
Jia-Fwu Shyu ◽  
Paik Seong Lim ◽  
Te-Chao Fang ◽  
Chien-Lin Lu ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Aryl Hydrocarbon Receptor ◽  
Critical Role ◽  
Osteoclast Differentiation ◽  
Indoxyl Sulfate ◽  
Raw 264.7 Cells ◽  
High Dose ◽  
Activated T Cells ◽  
Aryl Hydrocarbon

Indoxyl sulfate (IS) is a chronic kidney disease (CKD)-specific renal osteodystrophy metabolite that affects the nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), a transcription factor promoting osteoclastogenesis. However, the mechanisms underlying the regulation of NFATc1 by IS remain unknown. It is intriguing that the Aryl hydrocarbon receptor (AhR) plays a key role in osteoclastogenesis, since IS is an endogenous AhR agonist. This study investigates the relationship between IS concentration and osteoclast differentiation in Raw 264.7 cells, and examines the effects of different IS concentrations on NFATc1 expression through AhR signaling. Our data suggest that both osteoclastogenesis and NFATc1 are affected by IS through AhR signaling in both dose- and time-dependent manners. Osteoclast differentiation increases with short-term, low-dose IS exposure and decreases with long-term, high-dose IS exposure. Different IS levels switch the role of AhR from that of a ligand-activated transcription factor to that of an E3 ubiquitin ligase. We found that the AhR nuclear translocator may play an important role in the regulation of these dual functions of AhR under IS treatment. Altogether, this study demonstrates that the IS/AhR/NFATc1 signaling axis plays a critical role in osteoclastogenesis, indicating a potential role of AhR in the pathology and abnormality of bone turnover in CKD patients.

Role of the Aryl Hydrocarbon Receptor (AhR) in Mediating the Effects of Coffee in the Colon

2021 ◽  
pp. 2100539
Author(s):  
Robert S. Chapkin ◽  
Laurie A. Davidson ◽  
Hyejin Park ◽  
Un‐Ho Jin ◽  
Yang‐Yi Fan ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Aryl Hydrocarbon

Role of the Aryl Hydrocarbon Receptor in the Pathogenesis of Chronic Rhinosinusitis with Nasal Polyps

Inflammation ◽  
2013 ◽  
Vol 37 (2) ◽  
pp. 387-395 ◽  
Author(s):  
Ping Wei ◽  
Guo-hua Hu ◽  
Hou-yong Kang ◽  
Hong-bing Yao ◽  
Wei Kou ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Chronic Rhinosinusitis ◽  
Nasal Polyps ◽  
Aryl Hydrocarbon

scholarly journals Regulation of Estrogen Sulfotransferase Expression by Confluence of MCF10A Breast Epithelial Cells: Role of the Aryl Hydrocarbon Receptor

2011 ◽  
Vol 339 (2) ◽  
pp. 597-606 ◽  
Author(s):  
Jiaqi Fu ◽  
Hailin Fang ◽  
Michelle Paulsen ◽  
Mats Ljungman ◽  
Thomas A. Kocarek ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Aryl Hydrocarbon Receptor ◽  
Estrogen Sulfotransferase ◽  
Breast Epithelial Cells ◽  
Aryl Hydrocarbon ◽  
Breast Epithelial

scholarly journals Author response: Metabolic profiling during malaria reveals the role of the aryl hydrocarbon receptor in regulating kidney injury

2020 ◽  
Author(s):  
Michelle M Lissner ◽  
Katherine Cumnock ◽  
Nicole M Davis ◽  
José G Vilches-Moure ◽  
Priyanka Basak ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Metabolic Profiling ◽  
Kidney Injury ◽  
Author Response ◽  
Aryl Hydrocarbon

scholarly journals Immunotoxicity of Xenobiotics in Fish: A Role for the Aryl Hydrocarbon Receptor (AhR)?

2021 ◽  
Vol 22 (17) ◽  
pp. 9460
Author(s):  
Helmut Segner ◽  
Christyn Bailey ◽  
Carolina Tafalla ◽  
Jun Bo
Keyword(s):  
Immune System ◽  
Aryl Hydrocarbon Receptor ◽  
Disease Susceptibility ◽  
Immune Cell ◽  
Physiological Role ◽  
Immune Gene ◽  
Immune Systems ◽  
Aryl Hydrocarbon ◽  
The Impact

The impact of anthropogenic contaminants on the immune system of fishes is an issue of growing concern. An important xenobiotic receptor that mediates effects of chemicals, such as halogenated aromatic hydrocarbons (HAHs) and polyaromatic hydrocarbons (PAHs), is the aryl hydrocarbon receptor (AhR). Fish toxicological research has focused on the role of this receptor in xenobiotic biotransformation as well as in causing developmental, cardiac, and reproductive toxicity. However, biomedical research has unraveled an important physiological role of the AhR in the immune system, what suggests that this receptor could be involved in immunotoxic effects of environmental contaminants. The aims of the present review are to critically discuss the available knowledge on (i) the expression and possible function of the AhR in the immune systems of teleost fishes; and (ii) the impact of AhR-activating xenobiotics on the immune systems of fish at the levels of immune gene expression, immune cell proliferation and immune cell function, immune pathology, and resistance to infectious disease. The existing information indicates that the AhR is expressed in the fish immune system, but currently, we have little understanding of its physiological role. Exposure to AhR-activating contaminants results in the modulation of numerous immune structural and functional parameters of fish. Despite the diversity of fish species studied and the experimental conditions investigated, the published findings rather uniformly point to immunosuppressive actions of xenobiotic AhR ligands in fish. These effects are often associated with increased disease susceptibility. The fact that fish populations from HAH- and PAH-contaminated environments suffer immune disturbances and elevated disease susceptibility highlights that the immunotoxic effects of AhR-activating xenobiotics bear environmental relevance.

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