scholarly journals Gene Polymorphisms, Activation of the Aryl Hydrocarbon Receptor, and DNA Damage: A Preliminary Investigation

2018 ◽  
Author(s):  
Shadi Amini Nia ◽  
Giannina Satta ◽  
Grazianna Intranuovo ◽  
Sonia Sanna ◽  
Mariagrazia Zucca ◽  
...  
Keyword(s):  
Dna Damage ◽  
Aryl Hydrocarbon Receptor ◽  
Gene Polymorphisms ◽  
Preliminary Investigation ◽  
The Other ◽  
Luciferase Assay ◽  
Nucleotide Polymorphisms ◽  
Aryl Hydrocarbon ◽  
Non Hodgkin Lymphoma ◽  
Study Population

1) Background: We tested whether AHR activation induces DNA damage, whether polymorphisms in genes related to risk of Non-Hodgkin lymphoma are associated with DNA damage, and whether the two conditions do interact with each other. 2) Methods: Our study population included 36 subjects, randomly selected among the population controls participating in a case-control study on lymphoma in Sardinia, Italy, who donated a blood sample. We investigated 47 single nucleotide polymorphisms (SNPs) previously reported to convey risk of lymphoma; the Dual-Glo® Luciferase Assay System to detect activation of the aryl hydrocarbon receptor (AhR) by the serum of study subjects; and the COMET Assay to detect DNA damage. 3) Results: Activation of the aryl hydrocarbon receptor did not increase DNA damage in our study population. On the other hand, the mutant allele (G) of rs1056932/BCL6 increased the occurrence of DNA damage (p = 0.045); such association was confirmed among AhR negative, but not AhR positive subjects. 4) Conclusions: We observed excess DNA damage associated with a gene polymorphism, namely rs1056932/ BCL6, previously reported in association with risk of lymphoma. No increase in DNA damage was associated with AhR activation per se, nor with the other gene polymorphisms we investigated.

13C-caffeine breath test results show high dependence of aryl-hydrocarbon receptor SNPs

2020 ◽  
Author(s):  
Mchiko Ishii ◽  
Yukimoto Ishii ◽  
Tomohisa Nakayama ◽  
Yasuo Takahashi ◽  
Satoshi Asai
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Breath Test ◽  
Smoking Status ◽  
Area Under The Curve ◽  
Black Tea ◽  
Nucleotide Polymorphisms ◽  
Aryl Hydrocarbon ◽  
Significant Difference ◽  
Caffeine Metabolism ◽  
Characteristic Area

Abstract Aim: We investigated the relationship between trimethyl-13C-caffeine breath test (triCBT) and single nucleotide polymorphisms (SNPs) that are related to caffeine metabolism and consumption.Methods: Subjects were 132 young healthy adults (median 21 years: 101 male, 31 female). Subjects completed a questionnaire that enquired about their smoking status, consumption of caffeinated drinks (including coffee, black tea, green tea), height, weight, and body mass index (BMI). DNA was extracted from saliva, and genotyping was performed using TaqMan® SNP Genotyping for cytochrome P4501A2 rs762551, rs2472297, and aryl-hydrocarbon receptor rs4410790. Trimethyl 13C-caffeine (100 mg) was dissolved in distilled water and administered orally. Subsequently, breath samples were collected every 10 mins for 90 mins. Infrared spectroscopy was used to analyze the amount of 13CO2 in the expired breath, and the sum (Δ13CO2) over 90 min (S90m) was calculated.Results: All subjects had genotype CC for rs2472297. S90m was not significantly different among rs762551 genotypes; however, there was a significant difference in S90m among rs4410790 genotypes. Δ13CO2 was significantly affected by rs4410790 SNPs and smoking. The receiver operating characteristic area under the curve was 0.758 when rs4410790 phenotype C was considered positive. When the cutoff value was set to S90m (23.4 ‰), the sensitivity and specificity were 71.4% and 72.1%, respectively.Conclusions: Our results suggest that caffeine demethylation is affected by rs4410790 SNPs and smoking, and that triCBT can be used to identify SNPs in rs4410790.

scholarly journals Interleukin 33 Expression Induced by Aryl Hydrocarbon Receptor in Macrophages

2019 ◽  
Vol 170 (2) ◽  
pp. 404-414 ◽  
Author(s):  
Yasuhiro Ishihara ◽  
Thomas Haarmann-Stemmann ◽  
Norman Y Kado ◽  
Christoph F A Vogel
Keyword(s):  
Particulate Matter ◽  
Aryl Hydrocarbon Receptor ◽  
Airway Inflammation ◽  
Airborne Particulate Matter ◽  
Response To Treatment ◽  
Luciferase Assay ◽  
Interleukin 33 ◽  
Aryl Hydrocarbon ◽  
Polycyclic Aromatic ◽  
Mrna And Protein Expression

Abstract Polycyclic aromatic hydrocarbons (PAHs) contained in airborne particulate matter have been identified as a contributing factor for inflammation in the respiratory tract. Recently, interleukin-33 (IL-33) is strongly suggested to be associated with airway inflammation. Aryl hydrocarbon receptor (AhR) is a receptor for PAHs to regulate several metabolic enzymes, but the relationships between AhR and airway inflammation are still unclear. In this study, we examined the role of AhR in the expression of IL-33 in macrophages. THP-1 macrophages mainly expressed IL-33 variant 5, which in turn was strongly induced by the AhR agonists 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) and kynurenine (KYN). AhR antagonist CH223191 suppressed the increase in IL-33 expression. Promoter analysis revealed that the IL-33 promoter has 2 dioxin response elements (DREs). AhR was recruited to both DREs after treatment with TCDD or KYN as assessed by gel shift and chromatin immunoprecipitation assays. A luciferase assay showed that one of the DREs was functional and involved in the expression of IL-33. Macrophages isolated from AhR-null mice expressed only low levels of IL-33 even in response to treatment with AhR ligands compared with wild-type cells. The treatment of THP-1 macrophages with diesel particulate matter and particle extracts increased the mRNA and protein expression of IL-33. Taken together, the results show that ligand-activated AhR mediates the induction of IL-33 in macrophages via a DRE located in the IL-33 promoter region. AhR-mediated IL-33 induction could be involved in the exacerbation and/or prolongation of airway inflammation elicited by toxic chemical substances.

scholarly journals The Role of the Aryl Hydrocarbon Receptor (AHR) in Immune and Inflammatory Diseases

2018 ◽  
Vol 19 (12) ◽  
pp. 3851 ◽  
Author(s):  
Drew Neavin ◽  
Duan Liu ◽  
Balmiki Ray ◽  
Richard Weinshilboum
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Nuclear Receptor ◽  
Binding Sites ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Dependent Manner ◽  
Nucleotide Polymorphisms ◽  
Aryl Hydrocarbon ◽  
Inflammatory Processes ◽  
Targeted Gene Expression

The aryl hydrocarbon receptor (AHR) is a nuclear receptor that modulates the response to environmental stimuli. It was recognized historically for its role in toxicology but, in recent decades, it has been increasingly recognized as an important modulator of disease—especially for its role in modulating immune and inflammatory responses. AHR has been implicated in many diseases that are driven by immune/inflammatory processes, including major depressive disorder, multiple sclerosis, rheumatoid arthritis, asthma, and allergic responses, among others. The mechanisms by which AHR has been suggested to impact immune/inflammatory diseases include targeted gene expression and altered immune differentiation. It has been suggested that single nucleotide polymorphisms (SNPs) that are near AHR-regulated genes may contribute to AHR-dependent disease mechanisms/pathways. Further, we have found that SNPs that are outside of nuclear receptor binding sites (i.e., outside of AHR response elements (AHREs)) may contribute to AHR-dependent gene regulation in a SNP- and ligand-dependent manner. This review will discuss the evidence and mechanisms of AHR contributions to immune/inflammatory diseases and will consider the possibility that SNPs that are outside of AHR binding sites might contribute to AHR ligand-dependent inter-individual variation in disease pathophysiology and response to pharmacotherapeutics.

Aryl hydrocarbon receptor gene polymorphisms affect lung cancer risk

Lung Cancer ◽  
2007 ◽  
Vol 56 (1) ◽  
pp. 9-15 ◽  
Author(s):  
Jin Hee Kim ◽  
Heon Kim ◽  
Kye Young Lee ◽  
Jong-Won Kang ◽  
Kwan-Hee Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Risk ◽  
Aryl Hydrocarbon Receptor ◽  
Gene Polymorphisms ◽  
Lung Cancer Risk ◽  
Receptor Gene ◽  
Aryl Hydrocarbon ◽  
Receptor Gene Polymorphisms
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