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Smoking AND aryl hydrocarbon receptor (AHR)

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; levels of interleukin-22 (IL22) were measured by ELISA and smoking histories were collected...
October 18, 2016: Gastroenterology
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 DNA damages caused by NNK and its metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), O6-methylguanine (O6-mG) is likely the most carcinogenic in A/J mice. Results of our previous studies showed that O6-mG and other NNAL-derived DNA damages were preferentially reduced in the lung of female A/J mice upon the dietary treatment with dihydromethysticin (DHM), a promising lung cancer chemopreventive agent from kava...
October 11, 2016: Chemical Research in Toxicology
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
Prabagaran Esakky, Deborah A Hansen, Andrea M Drury, Paul Felder, Andrew Cusumano, Kelle H Moley
Paternal smoking is associated with infertility, birth defects and childhood cancers. Our earlier studies using cigarette smoke condensate (CSC) demonstrated several deleterious changes in male germ cells. Here, we hypothesize that chronic paternal exposure to CSC causes molecular and phenotypic changes in the sire and the offspring, respectively. In this mouse study, CSC caused DNA damage and cytotoxicity in testes via accumulation of benzo(a)pyrene (B[a]P) and cotinine. Decreased expression of growth arrest and DNA damage inducible alpha (Gadd45a), aryl hydrocarbon receptor (Ahr), and cyclin-dependent kinase inhibitor 1A (P21) was seen in CSC exposed testes...
October 2016: Reproductive Toxicology
Andrey Massarsky, Audrey J Bone, Wu Dong, David E Hinton, G L Prasad, Richard T Di Giulio
The zebrafish embryo has been proposed as a 'bridge model' to study the effects of cigarette smoke on early development. Previous studies showed that exposure to total particulate matter (TPM) led to adverse effects in developing zebrafish, and suggested that the antioxidant and aryl hydrocarbon receptor (AHR) pathways play important roles. This study investigated the roles of these two pathways in mediating TPM toxicity. The study consisted of four experiments. In experiment I, zebrafish embryos were exposed from 6h post fertilization (hpf) until 96hpf to TPM0...
October 15, 2016: Toxicology and Applied Pharmacology
Motoki Nakamura, Emi Nishida, Akimichi Morita
The aryl hydrocarbon receptor (AHR) mediates melanocyte activation and skin tanning. We hypothesized that the AHR also mediates melanoblast-to-melanocyte maturation. In a cloned cell line, NCCmelb4, derived from mouse neural crest cells, we investigated AHR expression in melanoblasts stimulated by UV irradiation and AHR agonists. We irradiated the cells with UV, ranging from 280 to 380 nm in 10-nm increments, using a multiwavelength irradiation spectral apparatus. Tyrosinase expression significantly increased with bimodal peaks at 310 and 360 nm...
August 2016: Experimental Dermatology
Anna Palatnik, Hong Xin, Emily J Su
INTRODUCTION: Maternal cigarette smoking is associated with elevated fetoplacental vascular resistance and fetal growth restriction (FGR). While studies have demonstrated varying effects of nicotine on blood flow, the role of polycyclic aromatic hydrocarbons (PAHs), abundant toxins in cigarette smoke that cross the placenta, has not been elucidated. We hypothesized that exposure of human fetoplacental endothelial cells (ECs) to the PAH benzo[a]yrene (BaP) would result in up-regulation of cyclooxygenase-2 (PTGS2) and preferential production of vasoconstrictive prostanoids via activation of the aryl hydrocarbon receptor (AHR) pathway...
August 2016: Placenta
Prabagaran Esakky, Kelle H Moley
Paternal exposure to constituents of cigarette smoke (CS) is reportedly associated with infertility, birth defects and childhood cancers even though the mechanism behind this relationship is still unclear. Chronic cigarette smoking by men leads to poor sperm quality and quantity mainly through oxidative stress and also direct assault by CS metabolites. Among several carcinogenic and teratogenic components of cigarette smoke condensate (CSC), polycyclic aromatic hydrocarbons (PAHs) display a preeminent role in accelerating germ cell death via the cytoplasmic transcription factor, aryl hydrocarbon receptor (AHR) that is present across all stages of spermatogenesis...
November 5, 2016: Molecular and Cellular Endocrinology
Nam Trung Nguyen, Taisuke Nakahama, Chi Hung Nguyen, Trang Thu Tran, Van Son Le, Hoang Ha Chu, Tadamitsu Kishimoto
Although rheumatoid arthritis (RA) is the most common autoimmune disease, affecting approximately 1% of the population worldwide, its pathogenic mechanisms are poorly understood. Tobacco smoke, an environmental risk factor for RA, contains several ligands of aryl hydrocarbon receptor (Ahr), also known as dioxin receptor. Ahr plays critical roles in the immune system. We previously demonstrated that Ahr in helper T-cells contributes to development of collagen-induced arthritis, a mouse model of RA. Other studies have shown that cigarette smoke condensate and pure Ahr ligands exacerbate RA by altering bone metabolism and inducing proinflammatory responses in fibroblast-like synoviocytes...
2015: Journal of Experimental Pharmacology
Martin Krøyer Rasmussen, Patrick Balaguer, Bo Ekstrand, Martine Daujat-Chavanieu, Sabine Gerbal-Chaloin
Skatole (3-methylindole) is a product of bacterial fermentation of tryptophan in the intestine. A significant amount of skatole can also be inhaled during cigarette smoking. Skatole is a pulmonary toxin that induces the expression of aryl hydrocarbon receptor (AhR) regulated genes, such as cytochrome P450 1A1 (CYP1A1), in human bronchial cells. The liver has a high metabolic capacity for skatole and is the first organ encountered by the absorbed skatole; however, the effect of skatole in the liver is unknown...
2016: PloS One
Chien-Hui Hong, Chih-Hung Lee, Hsin-Su Yu, Shau-Ku Huang
BACKGROUND: Atopic dermatitis (AD) is a common disease with genetic and environmental interactions. We previously reported lifetime exposure to cigarette smoke is associated with adult-onset AD. Aryl hydrocarbon receptor (AhR) is important in regulating environmental exposure to xenobiotics, including benzopyrenes (BP), a major polycyclic aromatic hydrocarbon (PAH) present in cigarette smoke. However, how AhR regulates immune responses in sensitization phase of AD remained elusive. METHODS: We investigated how BP affects epicutaneous sensitization response through AhR axis...
April 26, 2016: International Immunopharmacology
S Monnouchi, H Maeda, A Yuda, S Serita, N Wada, A Tomokiyo, A Akamine
BACKGROUND AND OBJECTIVE: Cigarette smoking has detrimental effects on periodontal tissue, and is known to be a risk factor for periodontal disease, including the loss of alveolar bone and ligament tissue. However, the direct effects of cigarette smoking on periodontal tissue remain unclear. Recently, we demonstrated that benzo[a]pyrene (BaP), which is a prototypic member of polycyclic aryl hydrocarbons and forms part of the content of cigarettes, attenuated the expression of extracellular matrix remodeling-related genes in human periodontal ligament (PDL) cells (HPDLCs)...
January 6, 2016: Journal of Periodontal Research
Miles Sarill, Michela Zago, Jared A Sheridan, Parameswaran Nair, Jason Matthews, Alvin Gomez, Lucie Roussel, Simon Rousseau, Qutayba Hamid, David H Eidelman, Carolyn J Baglole
The aryl hydrocarbon receptor (AhR) is a ubiquitously expressed receptor/transcription factor that mediates toxicological responses of environmental contaminants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Emerging evidence indicates that the AhR suppresses apoptosis and proliferation independent of exogenous ligands, including suppression of apoptosis by cigarette smoke, a key risk factor for chronic obstructive pulmonary disease (COPD). As cigarette smoke is a potent inducer of oxidative stress, a feature that may contribute to the development of COPD, we hypothesized that the AhR prevents smoke-induced apoptosis by regulating oxidative stress...
December 2015: Free Radical Biology & Medicine
Lindsay M Reynolds, Ma Wan, Jingzhong Ding, Jackson R Taylor, Kurt Lohman, Dan Su, Brian D Bennett, Devin K Porter, Ryan Gimple, Gary S Pittman, Xuting Wang, Timothy D Howard, David Siscovick, Bruce M Psaty, Steven Shea, Gregory L Burke, David R Jacobs, Stephen S Rich, James E Hixson, James H Stein, Hendrik Stunnenberg, R Graham Barr, Joel D Kaufman, Wendy S Post, Ina Hoeschele, David M Herrington, Douglas A Bell, Yongmei Liu
BACKGROUND: Tobacco smoke contains numerous agonists of the aryl hydrocarbon receptor (AhR) pathway, and activation of the AhR pathway was shown to promote atherosclerosis in mice. Intriguingly, cigarette smoking is most strongly and robustly associated with DNA modifications to an AhR pathway gene, the AhR repressor (AHRR). We hypothesized that altered AHRR methylation in monocytes, a cell type sensitive to cigarette smoking and involved in atherogenesis, may be a part of the biological link between cigarette smoking and atherosclerosis...
October 2015: Circulation. Cardiovascular Genetics
Heather H Burris, Andrea A Baccarelli, Hyang-Min Byun, Alejandra Cantoral, Allan C Just, Ivan Pantic, Maritsa Solano-Gonzalez, Katherine Svensson, Marcela Tamayo y Ortiz, Yan Zhao, Robert O Wright, Martha M Téllez-Rojo
Prenatal smoke exposure, maternal obesity, aberrant fetal growth, and preterm birth are all risk factors for offspring metabolic syndrome. Cord blood aryl-hydrocarbon receptor repressor (AHRR) DNA methylation is responsive to maternal smoking during pregnancy. AHRR serves not only to inhibit aryl-hydrocarbon receptor (AHR) transcription, which is involved in mediating xenobiotic metabolism, but it is also involved in cell growth and differentiation. Other than maternal smoking, other predictors of offspring AHRR DNA methylation status remain unknown; we sought to identify them among newborns...
2015: Epigenetics: Official Journal of the DNA Methylation Society
Francesca Toselli, Isabelle de Waziers, Mary Dutheil, Marc Vincent, Peter A Wilce, Peter R Dodd, Philippe Beaune, Marie-Anne Loriot, Elizabeth M J Gillam
1. Ethanol consumption and smoking alter the expression of certain drug-metabolizing enzymes and transporters, potentially influencing the tissue-specific effects of xenobiotics. 2. Amygdala (AMG) and prefrontal cortex (PFC) are brain regions that modulate the effects of alcohol and smoking, yet little is known about the expression of cytochrome P450 enzymes (P450s) and ATP-binding cassette (ABC) transporters in these tissues. 3. Here, we describe the first study on the expression of 19 P450s, their redox partners, three ABC transporters and four related transcription factors in the AMG and PFC of smokers and alcoholics by quantitative RT-PCR...
2015: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Erin L Hsu, Kevin Sonn, Abhishek Kannan, Sharath Bellary, Chawon Yun, Sohaib Hashmi, John Nelson, Marco Mendoza, Michael Nickoli, Jason Ghodasra, Christian Park, Sean Mitchell, Amruta Ashtekar, Anjan Ghosh, Akshay Jain, Stuart R Stock, Wellington K Hsu
BACKGROUND: Cigarette smoking inhibits bone-healing and leads to increased rates of pseudarthrosis. However, the mechanisms behind these effects are controversial. Dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin)--a cigarette smoke constituent and potent activator of the aryl hydrocarbon receptor (Ahr)--negatively impacts bone quality and osteoblast differentiation. We hypothesized that activation of the Ahr by dioxin would inhibit bone morphogenetic protein (BMP)-2-mediated spinal fusion in a rat arthrodesis model...
June 17, 2015: Journal of Bone and Joint Surgery. American Volume
P S S Rao, Santosh Kumar
High prevalence of cigarette smoking in HIV patients is associated with increased HIV pathogenesis and disease progression. While the effect of smoking on the occurrence of lung cancer has been studied extensively, the association between smoking and HIV pathogenesis is poorly studied. We have recently shown the possible role of cytochrome P450 (CYP) in smoking/nicotine-mediated viral replication. In this review, we focus on the potential role of CYP pathway in polycyclic aromatic hydrocarbons (PAH), important constituents of cigarette smoke, mediated HIV pathogenesis...
2015: Frontiers in Microbiology
Andreas Elentner, Daniela Ortner, Björn Clausen, Frank J Gonzalez, Pedro M Fernández-Salguero, Matthias Schmuth, Sandrine Dubrac
Skin is in daily contact with potentially harmful molecules from the environment such as cigarette smoke, automobile emissions, industrial soot and groundwater. Pregnane X receptor (PXR) is a transcription factor expressed in liver and intestine that is activated by xenobiotic chemicals including drugs and environmental pollutants. Topical application of the tumor initiator 7,12-dimethylbenz(a)anthracene (DMBA) enhances Pxr, Cyp1a1, Cyp1b1 and Cyp3a11, but not Ahr expression in the skin. Surprisingly, DMBA-induced Pxr upregulation is largely impaired in Langerin(+) cell-depleted skin, suggesting that DMBA mainly triggers Pxr in Langerin(+) cells...
November 2015: Experimental Dermatology
Shian Huang, Xiaorong Shui, Yuan He, Yiqiang Xue, Jianwen Li, Guoming Li, Wei Lei, Can Chen
The aryl hydrocarbon receptor (AhR) mediates the control of environmental toxicity, and modulates the development and pathogenesis of the cardiovascular system. However, little is known about the role of AhR in coronary arterial disease (CAD) susceptibility. We therefore conducted a case-control study in a Chinese population, and assessed the potential association between AhR variants and CAD susceptibility. Compared with the controls, circulating AhR expression was found to be significantly increased in patients with CAD and its subtypes including ST-segment and non-ST-segment elevation myocardial infarction, and stable and unstable angina pectoris...
2015: Scientific Reports
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