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Smoking AND aryl hydrocarbon receptor (AHR)

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
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...
December 13, 2016: Pharmacogenetics and Genomics
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
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
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), O(6)-methylguanine (O(6)-mG) is likely the most carcinogen in A/J mice. Results of our previous studies showed that levels of O(6)-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
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...
July 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)...
December 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
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