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Smoking AND aryl hydrocarbon receptor (AHR)

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https://www.readbyqxmd.com/read/29666259/shared-epitope-aryl-hydrocarbon-receptor-crosstalk-underlies-the-mechanism-of-gene-environment-interaction-in-autoimmune-arthritis
#1
Jiaqi Fu, Sarah V Nogueira, Vincent van Drongelen, Patrick Coit, Song Ling, Edward F Rosloniec, Amr H Sawalha, Joseph Holoshitz
The susceptibility to autoimmune diseases is affected by genetic and environmental factors. In rheumatoid arthritis (RA), the shared epitope (SE), a five-amino acid sequence motif encoded by RA-associated HLA-DRB1 alleles, is the single most significant genetic risk factor. The risk conferred by the SE is increased in a multiplicative way by exposure to various environmental pollutants, such as cigarette smoke. The mechanism of this synergistic interaction is unknown. It is worth noting that the SE has recently been found to act as a signal transduction ligand that facilitates differentiation of Th17 cells and osteoclasts in vitro and in vivo...
April 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29545172/benzo-a-pyrene-activates-an-ahr-src-erk-axis-that-contributes-to-cyp1a1-induction-and-stable-dna-adducts-formation-in-lung-cells
#2
G Vázquez-Gómez, L Rocha-Zavaleta, M Rodríguez-Sosa, P Petrosyan, J Rubio-Lightbourn
Benzo[a]pyrene (B[a]P), the most extensively studied carcinogen in cigarette smoke, has been regarded as a critical mediator of lung cancer. It is known that B[a]P-mediated Aryl hydrocarbon Receptor (AhR) activation stimulates the mitogen activated protein kinases (MAPK) signaling cascade in different cell models. MAPK pathway disturbances drive alterations in cellular processes, such as differentiation, proliferation, and apoptosis, and the disturbances may also modify the AhR pathway itself. However, MAPK involvement in B[a]P metabolic activation and toxicity in lung tissues is not well understood...
March 12, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29324662/aryl-hydrocarbon-receptor-antagonists-mitigate-the-effects-of-dioxin-on-critical-cellular-functions-in-differentiating-human-osteoblast-like-cells
#3
Chawon Yun, Karina M Katchko, Michael S Schallmo, Soyeon Jeong, Jonghwa Yun, Charlotte H Chen, Joseph A Weiner, Christian Park, Andrew George, Samuel I Stupp, Wellington K Hsu, Erin L Hsu
The inhibition of bone healing in humans is a well-established effect associated with cigarette smoking, but the underlying mechanisms are still unclear. Recent work using animal cell lines have implicated the aryl hydrocarbon receptor (AhR) as a mediator of the anti-osteogenic effects of cigarette smoke, but the complexity of cigarette smoke mixtures makes understanding the mechanisms of action a major challenge. 2,3,7,8-Tetrachlorodibenzo- p -dioxin (TCDD, dioxin) is a high-affinity AhR ligand that is frequently used to investigate biological processes impacted by AhR activation...
January 11, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29221954/total-particulate-matter-from-cigarette-smoke-disrupts-vascular-development-in-zebrafish-brain-danio-rerio
#4
Andrey Massarsky, G L Prasad, Richard T Di Giulio
Several studies have demonstrated zebrafish as a useful high-throughput in vivo model to study the effects of cigarette smoke on early development. It has been shown previously that exposure of zebrafish to cigarette smoke total particulate matter (TPM) leads to several adverse physiological aberrations, including heart deformities and improper angiogenesis. Consequently, this study investigated the effects of TPM on cardiovascular development in zebrafish that were exposed to increasing concentrations of TPM based upon nicotine content from 6h post fertilization (hpf) up to 72hpf...
January 15, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29185192/a-functional-aryl-hydrocarbon-receptor-genetic-variant-alone-and-in-combination-with-parental-exposure-is-a-risk-factor-for-congenital-heart-disease
#5
Silvia Pulignani, Andrea Borghini, Cecilia Vecoli, Ilenia Foffa, Lamia Ait-Ali, Maria Grazia Andreassi
Recent experimental studies showed that ablation of the aryl hydrocarbon receptor (AhR) as well as its activation by exogenous ligands disrupt the molecular networks involved in heart formation and function, leading to congenital heart disease (CHD). However, no evidence is available about the role of AhR in humans. We assessed the prevalence of a functional AhR genetic variant (p.Arg554Lys) in CHD patients as well as its joint effects with parental exposure. A total of 128 CHD patients (76 males; age 6.2 ± 6...
November 28, 2017: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/28971163/the-aryl-hydrocarbon-receptor-repressor-more-than-a-simple-feedback-inhibitor-of-ahr-signaling-clues-for-its-role-in-inflammation-and-cancer
#6
Christoph F A Vogel, Thomas Haarmann-Stemmann
The aryl hydrocarbon receptor repressor (AhRR) was first described as a specific competitive repressor of aryl hydrocarbon receptor (AhR) activity based on its ability to dimerize with the AhR nuclear translocator (ARNT) and through direct competition of AhR/ARNT and AhRR/ARNT complexes for binding to dioxin-responsive elements (DREs). Like AhR, AhRR belongs to the basic Helix-Loop-Helix/Per-ARNT-Sim (bHLH/PAS) protein family but lacks functional ligand-binding and transactivation domains. Transient transfection experiments with ARNT and AhRR mutants examining the inhibitory mechanism of AhRR suggested a more complex mechanism than the simple mechanism of negative feedback through sequestration of ARNT to regulate AhR signaling...
February 2017: Current Opinion in Toxicology
https://www.readbyqxmd.com/read/28749959/low-levels-of-the-ahr-in-chronic-obstructive-pulmonary-disease-copd-derived-lung-cells-increases-cox-2-protein-by-altering-mrna-stability
#7
Michela Zago, Jared A Sheridan, Hussein Traboulsi, Emelia Hecht, Yelu Zhang, Necola Guerrina, Jason Matthews, Parameswaran Nair, David H Eidelman, Qutayba Hamid, Carolyn J Baglole
Heightened inflammation, including expression of COX-2, is associated with chronic obstructive pulmonary disease (COPD) pathogenesis. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is reduced in COPD-derived lung fibroblasts. The AhR also suppresses COX-2 in response to cigarette smoke, the main risk factor for COPD, by destabilizing the Cox-2 transcript by mechanisms that may involve the regulation of microRNA (miRNA). Whether reduced AhR expression is responsible for heightened COX-2 in COPD is not known...
2017: PloS One
https://www.readbyqxmd.com/read/28674533/th17-polarization-under-hypoxia-results-in-increased-il-10-production-in-a-pathogen-independent-manner
#8
Roman Volchenkov, Vegard Nygaard, Zeynep Sener, Bjørn Steen Skålhegg
The IL-17-producing CD4(+) T helper cell (Th17) differentiation is affected by stimulation of the aryl hydrocarbon receptor (AhR) pathway and by hypoxia-inducible factor 1 alpha (HIF-1α). In some cases, Th17 become non-pathogenic and produce IL-10. However, the initiating events triggering this phenotype are yet to be fully understood. Here, we show that such cells may be differentiated at low oxygen and regardless of AhR ligand treatment such as cigarette smoke extract. Hypoxia led to marked alterations of the transcriptome of IL-10-producing Th17 cells affecting genes involved in metabolic, anti-apoptotic, cell cycle, and T cell functional pathways...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28481916/tcf21-and-the-environmental-sensor-aryl-hydrocarbon-receptor-cooperate-to-activate-a-pro-inflammatory-gene-expression-program-in-coronary-artery-smooth-muscle-cells
#9
Juyong Brian Kim, Milos Pjanic, Trieu Nguyen, Clint L Miller, Dharini Iyer, Boxiang Liu, Ting Wang, Olga Sazonova, Ivan Carcamo-Orive, Ljubica Perisic Matic, Lars Maegdefessel, Ulf Hedin, Thomas Quertermous
Both environmental factors and genetic loci have been associated with coronary artery disease (CAD), however gene-gene and gene-environment interactions that might identify molecular mechanisms of risk are not easily studied by human genetic approaches. We have previously identified the transcription factor TCF21 as the causal CAD gene at 6q23.2 and characterized its downstream transcriptional network that is enriched for CAD GWAS genes. Here we investigate the hypothesis that TCF21 interacts with a downstream target gene, the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor that mediates the cellular response to environmental contaminants, including dioxin and polycyclic aromatic hydrocarbons (e...
May 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28476168/dioxins-and-related-environmental-contaminants-increase-tdp-43-levels
#10
Peter E A Ash, Elizabeth A Stanford, Ali Al Abdulatif, Alejandra Ramirez-Cardenas, Heather I Ballance, Samantha Boudeau, Amanda Jeh, James M Murithi, Yorghos Tripodis, George J Murphy, David H Sherr, Benjamin Wolozin
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative condition that is characterized by progressive loss of motor neurons and the accumulation of aggregated TAR DNA Binding Protein-43 (TDP-43, gene: TARDBP). Increasing evidence indicates that environmental factors contribute to the risk of ALS. Dioxins, related planar polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons (PAHs) are environmental contaminants that activate the aryl hydrocarbon receptor (AHR), a ligand-activated, PAS family transcription factor...
May 5, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28377982/mechanistic-insight-into-the-effects-of-aryl-hydrocarbon-receptor-activation-on-osteogenic-differentiation
#11
Chawon Yun, Joseph A Weiner, Danielle S Chun, Jonghwa Yun, Ralph W Cook, Michael S Schallmo, Abhishek S Kannan, Sean M Mitchell, Ryan D Freshman, Christian Park, Wellington K Hsu, Erin L Hsu
While inhibition of bone healing and increased rates of pseudarthrosis are known adverse outcomes associated with cigarette smoking, the underlying mechanisms by which this occurs are not well understood. Recent work has implicated the Aryl Hydrocarbon Receptor (Ahr) as one mediator of the anti-osteogenic effects of cigarette smoke (CS), which contains numerous toxic ligands for the Ahr. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) is a high-affinity Ahr ligand frequently used to evaluate Ahr pathway activation...
June 2017: Bone Reports
https://www.readbyqxmd.com/read/28285017/effects-of-the-aryl-hydrocarbon-receptor-agonist-3-methylcholanthrene-on-the-17%C3%AE-estradiol-regulated-mrna-transcriptome-of-the-rat-uterus
#12
Janina Helle, Annekathrin M Keiler, Oliver Zierau, Peggy Dörfelt, Günter Vollmer, Leane Lehmann, Sridar V Chittur, Martin Tenniswood, JoEllen Welsh, Georg Kretzschmar
Polycyclic aromatic hydrocarbons (PAHs) are products of incomplete combustion of organic compounds, abundant in exhaust fumes and cigarette smoke. They act by binding to the aryl hydrocarbon receptor (AHR) which induces expression of phase 1 and phase 2 enzymes in the liver. PAH induced AHR activation may also lead to adverse effects by modulating other pathways, for example estrogen receptor (ER) signaling in the female reproductive tract. We have investigated the effects of the PAH 3-methylcholanthrene (3-MC) on 17β-estradiol (E2) dependent signaling in the uterus of ovariectomized rats to characterize the cross talk between AHR and ER on an mRNA transcriptome wide scale...
July 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28254546/relb-attenuates-cigarette-smoke-extract-induced-apoptosis-in-association-with-transcriptional-regulation-of-the-aryl-hydrocarbon-receptor
#13
Matthew Iu, Michela Zago, Angela Rico de Souza, Manuella Bouttier, Swati Pareek, John H White, Qutayba Hamid, David H Eidelman, Carolyn J Baglole
Chronic obstructive pulmonary disease (COPD) is a chronic and prevalent respiratory disease caused primarily by long term inhalation of cigarette smoke. A major hallmark of COPD is elevated apoptosis of structural lung cells including fibroblasts. The NF-κB member RelB may suppress apoptosis in response to cigarette smoke, but its role in lung cell survival is not known. RelB may act as a pro-survival factor by controlling the expression of superoxide dismutase 2 (SOD2). SOD2 is also regulated by the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor that suppresses cigarette smoke-induced apoptosis...
February 27, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28249752/benzo-a-pyrene-impedes-self-renewal-and-differentiation-of-mesenchymal-stem-cells-and-influences-fracture-healing
#14
Yiqing Zhou, Rong Jiang, Liqin An, Hong Wang, Sicheng Cheng, Shi Qiong, Yaguang Weng
Mesenchymal stem cells (MSCs) are implicated in the bone-forming process during fracture repair. Benzo[a]pyrene (BaP)-a cigarette smoke component and powerful motivator of the aryl hydrocarbon receptor (Ahr)-unfavorably influences bone condition and osteoblast differentiation. The first thing we noticed decreases self-renewal and differentiation of human bone marrow mesenchymal stem (hBM-MSCs) from smokers and activates Ahr signaling in MSCs by up-regulating the Ahr target gene cytochrome P450 (CYP) 1B1 expression...
June 1, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28079158/aryl-hydrocarbon-receptor-ahr-dependent-regulation-of-pulmonary-mirna-by-chronic-cigarette-smoke-exposure
#15
Sarah Rogers, Angela Rico de Souza, Michela Zago, Matthew Iu, Necola Guerrina, Alvin Gomez, Jason Matthews, Carolyn J Baglole
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor historically known for its toxic responses to man-made pollutants such as dioxin. More recently, the AhR has emerged as a suppressor of inflammation, oxidative stress and apoptosis from cigarette smoke by mechanisms that may involve the regulation of microRNA. However, little is known about the AhR regulation of miRNA expression in the lung in response to inhaled toxicants. Therefore, we exposed Ahr(-/-) and Ahr(+/-) mice to cigarette smoke for 4 weeks and evaluated lung miRNA expression by PCR array...
January 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/27977510/a-comprehensive-contribution-of-genes-for-aryl-hydrocarbon-receptor-signaling-pathway-to-hypertension-susceptibility
#16
Alexey V Polonikov, Olga Yu Bushueva, Irina V Bulgakova, Maxim B Freidin, Mikhail I Churnosov, Maria A Solodilova, Yaroslav D Shvetsov, Vladimir P Ivanov
OBJECTIVE: The present study was designed to investigate whether genetic polymorphisms of the aryl hydrocarbon receptor (AHR) signaling pathway are involved in the molecular basis of essential hypertension (EH). METHODS: A total of 2160 unrelated Russian individuals comprising 1341 EH patients and 819 healthy controls were recruited into the study. Seven common AHR pathway single-nucleotide polymorphisms (SNPs) such as rs2066853, rs2292596, rs2228099, rs1048943, rs762551, rs1056836, and rs1800566 were genotyped by TaqMan-based allele discrimination assays...
February 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/27849171/the-nuclear-receptor-ahr-controls-bone-homeostasis-by-regulating-osteoclast-differentiation-via-the-rank-c-fos-signaling-axis
#17
Takashi Izawa, Rieko Arakaki, Hiroki Mori, Takaaki Tsunematsu, Yasusei Kudo, Eiji Tanaka, Naozumi Ishimaru
The aryl hydrocarbon receptor (AhR) pathway plays a key role in receptor activator of NF-κB ligand (RANKL)-mediated osteoclastogenesis. However, the mechanism underlying the regulation of AhR expression in osteoclasts and the signaling pathway through which AhR controls osteoclastogenesis remain unclear. We found that the expression of AhR in bone marrow-derived osteoclasts was upregulated by RANKL at an earlier stage than was the expression of signature osteoclast genes such as those encoding cathepsin K and NFAT, cytoplasmic, calcineurin-dependent 1...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27769811/aryl-hydrocarbon-receptor-ligands-in-cigarette-smoke-induce-production-of-interleukin-22-to-promote-pancreatic-fibrosis-in-models-of-chronic-pancreatitis
#18
Jing Xue, Qinglan Zhao, Vishal Sharma, Linh P Nguyen, Yvonne N Lee, Kim L Pham, Mouad Edderkaoui, Stephen J Pandol, Walter Park, Aida Habtezion
BACKGROUND & AIMS: Cigarette smoke has been identified as an independent risk factor for chronic pancreatitis (CP). Little is known about the mechanisms by which smoking promotes development of CP. We assessed the effects of aryl hydrocarbon receptor (AhR) ligands found in cigarette smoke on immune cell activation in humans and pancreatic fibrosis in animal models of CP. METHODS: We obtained serum samples from patients with CP treated at Stanford University hospital and healthy individuals (controls) and isolated CD4+ T cells...
December 2016: Gastroenterology
https://www.readbyqxmd.com/read/27728767/dihydromethysticin-dhm-blocks-tobacco-carcinogen-4-methylnitrosamino-1-3-pyridyl-1-butanone-nnk-induced-o-6-methylguanine-in-a-manner-independent-of-the-aryl-hydrocarbon-receptor-ahr-pathway-in-c57bl-6-female-mice
#19
Sreekanth C Narayanapillai, Shang-Hsuan Lin, Pablo Leitzman, Pramod Upadhyaya, Carolyn J Baglole, Chengguo Xing
4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a key carcinogen responsible for tobacco smoke-induced lung carcinogenesis. Among the types of DNA damage caused by NNK and its metabolite, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), O6 -methylguanine (O6 -mG) is likely the most carcinogen in A/J mice. Results of our previous studies showed that levels of O6 -mG and other types of NNAL-derived DNA damage were preferentially reduced in the lung of female A/J mice upon dietary treatment with dihydromethysticin (DHM), a promising lung cancer chemopreventive agent from kava...
November 21, 2016: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/27598741/a-promoter-variant-within-the-aryl-hydrocarbon-receptor-gene-is-associated-with-an-epithelial-barrier-defect-in-smokers-with-crohn-s-disease
#20
Matthias Prager, Janine Büttner, Philip Grunert, David Ellinghaus, Carsten Büning
BACKGROUND: Smoking worsens Crohn's disease (CD). The aryl hydrocarbon receptor (AhR) is a transcription factor that mediates the toxicity of dioxinlike chemicals. We hypothesized that AHR variants and smoking influence CD. METHODS: Exon-intron boundaries and coding and promoter regions of AHR gene were sequenced (28 patients with inflammatory bowel disease; 4 healthy controls). Two identified variants (rs7796976 and rs2066853) were studied for an association with intestinal permeability (IP, oral sugar test) in patients with inflammatory bowel disease (stratified according to the smoking status)...
October 2016: Inflammatory Bowel Diseases
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