Abstract Cytochrome P450 (CYP) enzymes are the major metabolizers of xenobiotics, e.g. drugs, and environmental toxins. Thus, changes in CYP expression have an important impact on drug metabolism and susceptibility to chemical toxicity. In the present study, the transcriptional mechanisms of both constitutive and inducible regulation of the Cyp2a5 gene in mouse liver were investigated. Mouse primary hepatocyte cultures were used as the main model system together with cell and molecular biology methods. The key activation regions of the Cyp2a5 5' promoter were determined using reporter gene assays. Two major transcription activation sites of the Cyp2a5 5' promoter, called the proximal and the distal, were found. Transcription factors hepatocyte nuclear factor-4 (HNF-4) and nuclear factor I were shown to bind to the proximal promoter. Aryl hydrocarbon receptor nuclear translocator (ARNT) and upstream stimulatory factor bound to a common palindromic E-box element in the distal promoter region. All three response elements were shown to be essential for constitutive expression of CYP2A5 in murine hepatocytes. ARNT appeared to control Cyp2a5 transcription without a heterodimerization partner suggesting active involvement of the ARNT homodimer in mammalian gene regulation. Aryl hydrocarbon receptor (AHR) ligands were shown to induce Cyp2a5 transcriptionally by an AHR-dependent mechanism, and established Cyp2a5 as a novel AHR-regulated gene. The AHR response element and the E-box, identified in these studies, were located near to each other and close to a separately defined nuclear factor (erythroid-derived 2)-like 2 binding site in the distal region of the Cyp2a5 promoter, suggesting cooperation between these elements. Peroxisome proliferator-activated receptor gamma coactivator-1α was shown to up-regulate Cyp2a5 transcription through coactivation of HNF-4α. This indicates that xenobiotic metabolism can be regulated by modification of co-activation. The present results show that CYP2A5 is regulated by several different cross-regulatory pathways. The regulatory mechanisms involved in the transcription of the Cyp2a5 gene may also control other CYP genes, especially the human ortholog CYP2A6, and may explain some of the individual variations in the metabolism of xenobiotics.

A large percentage of oil and gas reservoirs in the most productive regions such as the Middle East, South America, and Southeast Asia are naturally fractured reservoirs (NFR). The major difference between conventional reservoirs and naturally fractured reservoirs is the discontinuity in media in fractured reservoir due to tectonic activities. These discontinuities cause remarkable difficulties in describing the petrophysical structures and the flow of fluids in the fractured reservoirs. Predicting fluid flow behavior in naturally fractured reservoirs is a challenging area in petroleum engineering. Two classes of models used to describe flow and transport phenomena in fracture reservoirs are discrete and continuum (i.e. dual porosity) models. The discrete model is appealing from a modeling point of view, but the huge computational demand and burden of porting the fractures into the computational grid are its shortcomings. The affect of natural fractures on the permeability anisotropy can be determined by considering distribution and orientation of fractures. Representative fracture permeability, which is a crucial step in the reservoir simulation study, must be calculated based on fracture characteristics. The diagonal representation of permeability, which is customarily used in a dual porosity model, is valid only for the cases where fractures are parallel to one of the principal axes. This assumption cannot adequately describe flow characteristics where there is variation in fracture spacing, length, and orientation. To overcome this shortcoming, the principle of the full permeability tensor in the discrete fracture network can be incorporated into the dual porosity model. Hence, the dual porosity model can retain the real fracture system characteristics. This study was designed to develop a novel approach to integrate dual porosity model and full permeability tensor representation in fractures. A fully implicit, parallel, compositional chemical dual porosity simulator for modeling naturally fractured reservoirs has been developed. The model is capable of simulating large-scale chemical flooding processes. Accurate representation of the fluid exchange between the matrix and fracture and precise representation of the fracture system as an equivalent porous media are the key parameters in utilizing of dual porosity models. The matrix blocks are discretized into both rectangular rings and vertical layers to offer a better resolution of transient flow. The developed model was successfully verified against a chemical flooding simulator called UTCHEM. Results show excellent agreements for a variety of flooding processes. The developed dual porosity model has further been improved by implementing a full permeability tensor representation of fractures. The full permeability feature in the fracture system of a dual porosity model adequately captures the system directionality and heterogeneity. At the same time, the powerful dual porosity concept is inherited. The implementation has been verified by studying water and chemical flooding in cylindrical and spherical reservoirs. It has also been verified against ECLIPSE and FracMan commercial simulators. This study leads to a conclusion that the full permeability tensor representation is essential to accurately simulate fluid flow in heterogeneous and anisotropic fracture systems. / text

<p>This research was aimed at employing the broad use of petrophysical analysis and reservoir modelling techniques to explore the petroleum resources in the sandstone units of deep marine play in the Bredasdorp Basin.</p>

Crude oil is of economic importance to any nation. However its poor management and disposal method has resulted in oil spillage and ground contamination. Most emphasis on crude oil contamination on the environment has been on surface and ground water pollution, as well as plants and animals with little or no attention paid to the engineering properties of the contaminated soil. This research is thus aimed at investigating the effect of light crude oil contamination on the geotechnical properties of kaolinite clay soil. This research is a laboratory based experiment in which the contaminated soil was prepared by adding different percentages of light crude oil (2%, 5%, 8%, 10%, 15% and 20%) measured by weight of the dry soil sample and mixed until a uniform mixture was obtained. The British Standard Test Methods for Civil Engineering purposes BS 1377: 1990 (EUROCODE 7: EN 1997: 2-5) was adopted with few modifications. The calculations were based on the fact that the pore space in the contaminated soil is occupied by water and crude oil so water content was calculated from the fluid content and the rate of evaporation of crude oil during oven drying was also considered. The classification results showed that crude oil contamination caused an increase in linear shrinkage, liquid limit, plastic limit and plasticity index between 0% to 20% contaminations. The compaction result showed that there was an increase in maximum dry density while the optimum moisture content decreased between 0% and 15% of crude oil contamination. The result showed that the soil could not compact at 20% contamination and above. Also, the coefficient of permeability increased with increase in the percentage of crude oil contamination while the coefficient of consolidation value (Cv) increases with increase in the percentage of contamination. There was a decrease in the cohesion value and the frictional angle due to the introduction of the crude oil into the soil. Although crude oil altered the geotechnical properties of the kaolinite clay soil and reduced its strength, the soil can still be used for geotechnical purposed after remediation.

Introdução: A artrite reumatóide (AR) é uma artropatia autoimune, de caráter inflamatório, com prevalência em torno de 1% da população. O tabagismo é considerado o principal fator de risco para o desenvolvimento da AR. O receptor de hidrocarbonetos de arila (AhR), um fator de transcrição intracelular ativado por hidrocarbonetos aromáticos componentes da fumaça do cigarro, foi identificado como alvo de regulação da diferenciação de células Th17. Objetivos: Avaliar se os polimorfismos genéticos do AhR estariam associados ao desenvolvimento da AR , e se este receptor estaria mais expresso em pacientes com AR. Pacientes e Métodos: Nós analisamos sete polimorfismos genéticos por mudança de única base (SNP) por PCR em tempo real utilizando sondas TaqMan em 138 pacientes com AR e 129 indivíduos saudáveis. A quantificação da expressão do mRNA do AhR em células mononucleares isoladas de pacientes com AR e indivíduos saudáveis foi realizada por PCR em tempo real. Resultados: Identificamos que haplótipos formados por SNPs no AhR estariam associados com desenvolvimento da AR, podendo ser fator protetor ou de risco para a doença. Em adição, os pacientes com haplótipos de risco apresentavam doença com índice de atividade elevado, principalmente quando o tabagismo estava presente. De fato, pacientes com AR apresentaram aumento na expressão de AhR (mRNA) em relação a indivíduos saudáveis. Conclusões: Em conjunto estes resultados sugerem que o AhR possui um papel importante para o desenvolvimento da artrite reumatóide. Possivelmente mutações neste receptor podem estar relacionadas com alterações na sua atividade e conseqüentemente na diferenciação de células Th17 e a susceptibilidade a AR. / Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune arthropaty with inflammatory characteristics and prevalence around 1% in the population. Tabagism is the main risk factor to RA development. The aryl hydrocarbon receptor (AhR) is an intracellular transcription factor activated by aromatic hydrocarbons present in smoking, whichwas identified to be a target of regulation of Th17 differentiation. Purpose: Study the relationship of genetic polymorphisms in AhR with RA development, and if this receptor expression is upregulated in RA patients. Patients and Methods: We analyzed seven genetic single nucleotide polymorphisms by Real-Time PCR using TaqMan probes in 138 patients with Rheumatoid Arthritis and 129 healthy controls. The AhR mRNA quantization in mononuclear cells isolated from AR patients and healthy controls has been done by Realt-Time PCR. Results: We identified that AhR haplotypes were associated with RA development and that they could be protector or risk factors to disease. In addition, patients with risk haplotypes showed higher disease activity index, mainly when smoking was present. Indeed, patients with RA showed upregulation in the AhR expression (mRNA) when compared with healthy controls. Conclusions: These results suggest that AhR has an important role in AR development. Probably, mutations in this receptor could be related with alterations in its activity and consequently in the differentiation of Th17 cells and RA susceptibility.

A citometria de fluxo é um método preciso, rápido e eficaz na avaliação de múltiplos parâmetros celulares, tanto estruturais como funcionais, propiciando a separação e o estudo de diferentes populações e sub-populações de células. No presente estudo, foram empregados métodos citométricos para caracterização dos diferentes tipos celulares sangüíneos de Centropomus parallelus, assim como para verificação da viabilidade celular, avaliação da atividade fagocítica e ativação do burst respiratório. Foram identificadas três sub-populações representativas de leucócitos: linfócitos, monócitos e trombócitos. Estas células foram estimuladas, in vitro, com Staphylococcus aureus, marcado com iodeto de propídeo (SAPI), lipopolissacarídeo de Escherichia coli (LPS) e zymosan, partículas de Saccharomyces cerevisiae. As respostas frente aos estímulos foram distintas de acordo com o tipo celular e o estímulo apresentado. Os monócitos apresentaram maiores percentuais de fagocitose frente ao estímulo provocado pela SAPI e pelo Zymosan; já a população que continha trombócitos entre outros tipos celulares (por exemplo: linfócitos), apresentou \"fagocitose\" significativa apenas para SAPI. O burst oxidativo detectado pela fluorescência emitida pelo diacetato 2´7´diclorofluoresceína (DCFH) foi significativo apenas quando estimulado com PMA (miristato-acetato de forbol), não apresentando resposta estatisticamente significante para os estímulos SAPI e LPS. Após a exposição ao naftaleno nas concentrações 10-3, 10-6, 10-9 M durante quatro horas, in vitro, houve um aumento na fagocitose realizado pelos monócitos e trombócitos, porém uma diminuição no burst oxidativo apresentado nas concentrações 10-6 e 10-9 M de naftaleno. Este resultado reflete, in vitro, uma resposta ao contaminante com significado imunológico desfavorável para o peixe, já que as células estão aumentando a atividade fagocítica sem conseguirem, teoricamente, destruir o agente invasor. A partir desses resultados preliminares, podemos avaliar melhor, algumas características da resposta imune inata desta espécie de peixe, presente na costa litorânea brasileira. Estes parâmetros imunofisiológicos podem servir como base para futuros estudos ecotoxicológicos tanto em laboratório mas também a campo. Estudos que utilizam a imunidade inata como indicador biológico de alterações ambientais causadas por poluentes diversos, podem evidenciar o grau de impacto toxicológico sobre esta espécie e agregar valor a sua importância econômica e ecológica. / Flow cytometry is a precise, fast, and effective method for the evaluation of several cellular parameters, both structural and functional, allowing the sorting and analysis of particular populations and sub-populations of cells. In this study, we employed cytometric methods on the caractherization of different blood cell types from Centropomus parallelus, and also verified cell viability, phagocytic activity and oxidative burst in these cells. Three sub-populations were identified: lymphocytes, monocytes, and trombocytes. These cells were stimulated in vitro with propidium iodide-conjugated Staphylococcus aureus (SAPI), Escherichia coli lipopolysaccharide (LPS), or zymosan (Saccharomyces cerevisae particles). Responses to each individual stimulus differed according to cell type. Monocytes displayed the higher percentages of phagocytosis in presence of SAPI or zymosan; on the other hand, the population that included trombocytes, among other cell types (such as lymphocytes) only performed phagocytosis in a relevant level in the presence of SAPI. The oxidative burst, detected by fluorescence emitted by 2´7´dichlorofluorescein diacetate (DCFH) was significant only after stimulation with PMA (phorbol myristate-acetate), but not when the stimulus was SAPI or LPS. Based on these preliminary results, the innate immune response in these animals (ubiquitous coastal waters of the Brazilian shore) can be further evaluated. Immunophysiological parameters in these species can build a solid ground for future ecotoxicological studies. Approaching innate immunity as a biological indicator of environmental changes induced by pollutants may support the degree of toxicological impact over these animals, and aggregate value to its current ecological and economical importance.

Investigar, em motores veiculares pesados, alimentados com combustível diesel, a emissão de dioxinas e furanos clorados (PCDD/Fs) e hidrocarbonetos policíclicos aromáticos (PAHs), através da análise de material particulado e gases do sistema de exaustão. Investigar a mutagenicidade do material particulado e gases coletados. Material e Métodos: Os testes de emissão foram feitos em banco de provas dinamométrico de bancada de acordo com Ciclo 13 Pontos de testes, utilizando-se motores Diesel nacionais de aplicação veícular. Um mini-túnel de diluição foi usado para obtenção de amostras de material particulado. As análises de PCDD/Fs e PAHs foram realizadas em laboratório nacional. Para a análise de PCDD/Fs utilizou-se o método USEPA 8290 (1994) e para a análise de PAHs foi utilizado o método USEPA TO 13A (1999). A análise de mutagenicidade foi realizada de acordo com o Teste de Ames (TA98). Resultados: As medições de PCDD/Fs indicaram em geral valores abaixo do limite de detecção do método analítico. Em uma das amostras foi verificado que o OCDD ficou acima do limite de detecção, enquanto em outra isto ocorreu para o OCDF e para o 1,2,3,7,8-PeCDF. Em relação aos PAHs analisados verificou-se a presença dos seguintes compostos: Naftaleno, Acenaftileno, Acenafteno, Fluoreno, Fenantreno, Antraceno, Fluoranteno, Pireno, Benzo[a]antraceno, Criseno, Benzo[b]fluoranteno, Benzo[k]fluoranteno. A média encontrada para 5 amostras analisadas foi de 3.580,5 µg/g de material particulado. Os PAHs encontrados neste trabalho indicam alguma similaridade com a literatura disponível, para valores em % e µg/g de material particulado total coletado. O teste de Ames indicou que o material particulado coletado de motores diesel tem alta atividade mutagênica. Conclusões: A emissão de PCDD/Fs, para o nível de tecnologia dos motores Diesel testados mostrou-se pouco significativa, considerando-se combustível conforme especificado e método e limite de detecção utillizados. Em relação aos PAHs, os resultados indicaram que motores diesel têm uma contribuição importante na formação destes compostos. A alta atividade mutagênica observada mostra que as emissões de veículos Diesel são potencialmente tóxicas. Recomenda-se a continuidade de estudos para definição da regulamentação desses poluentes. / To investigate emission of chlorinated dioxins and furans (PCDD/Fs) and polycyclic aromatic hydrocarbons (PAHs) in heavy duty diesel engines, through the analysis of particulate material and gases in the exhaust.To verify mutagenicity of collected particulate material and gasesous sample extracts. Material and Methods: The engine emissions tests were done in dynamometer test bench according to 13-Mode Cycle, using brazilian engines, vehicle application. A mini dilution tunnel was used to obtain particulate matter and gaseous sample. PCDD/Fs and PAHs analyses were carried out in a certified national laboratory. Dioxins and furans were analyzed according with Method 8290 (USEPA, 1994) and PAHs by Method TO13A (USEPA, 1999). The mutagenicity analyses were done in accordance with Ames test (TA98) Results: The measurements of dioxins and furans in diesel engines operating in controlled conditions in dynamomter bench test, had indicated emissions values in general below the detention limit of the analytical method. In one of the samples it was verified that the OCDD was above the detention limit, while in another one this occurred for OCDF and 1,2,3,7,8-PeCDF. In relation to 16 PAHs it was verified the presence of the following compounds: Naphthalene, Acenaphthylene, Acenaphthene, Fluorene, Phenanthrene, Antracene, Fluorantene, Pyrene, Benzo[a]antracene, Chrysene, Benzo[b]fluoranthene and Benzo[k]fluorantene. The average value of the sum of PAHs found in five samples was 3,580.5 µg.g-1. The PAHs found in this study indicates some similarity with available literature for values in % and µg/g of particulate matter.The Ames test showed that the collected particulate material from diesel engines presents high mutagenic activity. Conclusion: The emission of PCDD/Fs, for the level of technology of the tested Diesel engines revealed little significant, considering the specified fuel, method of analysis and limit of detention used. In relation to the 16 PAHs, the tests results had indicated that diesel engines has an important contribution in the formation of these compounds. The high mutagenic activity observed shows that the emissions of Diesel vehicles are potentially toxic. The continuity of studies for definition of the regulation of these pollutants is recommended.

Le récepteur aux hydrocarbures aromatiques (AhR) est un facteur de transcription activé par de nombreux xénobiotiques (molécules étrangères à l’organisme) qui régule l’expression d’enzymes et transporteurs permettant le métabolisme et l’élimination de ces ligands. Cette protéine exprimée dans toutes les cellules chez les vertébrés, joue un rôle majeur dans la détoxication et la protection des organismes vis à vis des molécules toxiques. Des orthologues de celle-ci ont été identifiés chez les invertébrés mais ne semblent pas jouer le même rôle; ils sont exprimés principalement dans des neurones et ne sont pas activés par des polluants. L’absence du AhR chez ces organismes entraîne au niveau cellulaire, des défauts de morphologie dendritique et sur le plan comportemental, des anomalies dans le comportement de nutrition. Malgré ces découvertes, peu de recherches ont été entreprises sur les conséquences d’une invalidation du AhR sur le fonctionnement du système nerveux central chez les vertébrés. Au cours de ma thèse, j’ai étudié ces conséquences au niveau moléculaire, cellulaire et comportemental: les souris AhR KO développent un nystagmus pendulaire horizontal dont l’origine est en partie liée à des défauts structuraux de la gaine de myéline. Au niveau moléculaire, nous avons mis en évidence un changement de la composition lipidique, de l’expression des gènes de la myéline et de l’inflammation, défauts qui sont retrouvés en partie chez des souris dont le AhR a été invalidé spécifiquement dans l’oligodendrocyte, la cellule responsable de la formation de la gaine de myéline. J’ai donc réalisé des études en parallèle sur la lignée murine d’oligodendrocyte, 158N, et montré que l’invalidation du AhR dans cette lignée ainsi que in vivo, modifiait l’expression du gène MAG (Myelin Associated Glycoprotein). Compte tenu du rôle du AhR en tant que récepteur de polluants, nous avons également exposé ou traité nos modèles avec de la TCDD (dioxine de Seveso) et montré que celle-ci modifiait également l’expression du gène MAG. Mes travaux démontrent donc que le AhR joue un rôle au niveau oligodendrocytaire dans la formation de la gaine de myéline. Son rôle connu en tant que récepteur de polluants laisse supposer que certaines contaminations environnementales pourraient jouer un rôle dans l’incidence de pathologies au niveau du système nerveux central, ce qui soulève de nombreuses questions en terme de santé publique. / The aryl hydrocarbon receptor (AhR) is a transcription factor activated by many xenobiotics (foreign molecules) that regulates the expression of enzymes and transporters which allow the metabolism and elimination of these ligands. This protein expressed in all cells in vertebrates, plays a major role in detoxication and protection of the organisms against toxic molecules. Some orthologs have been identified in invertebrates but do not seem to play the same role; they are expressed mainly in neurons and are not activated by pollutants. The absence of the AhR in these organisms causes at the cellular level, defects of the dendritic morphology and behaviourally, abnormalities in the feeding behavior. Despite these findings, little research has been conducted on the consequences of the AhR invalidation in the central nervous system of vertebrates. During my PhD, I studied these consequences at the molecular, cellular and behavioral : the AhR knockout mice develop a horizontal pendular nystagmus whose origin is partly related to structural defects in the myelin sheath. At the molecular level, we have shown modifications in the lipid composition, myelin and inflammation gene expression, defects that are found partly in mice whose AhR was invalidated specifically in the oligodendrocytes, the cells involved in myelin sheath formation. I therefore made parallel studies on the murine oligodendrocyte lineage, 158N, and showed that the invalidation of the AhR in this cell line and in vivo, altered MAG (Myelin Associated Glycoprotein) gene expression. Given the role of the AhR as a receptor of pollutants, we have also exposed or treated our models with TCDD (dioxin of Seveso) and showed that it also changed the expression of MAG gene. My works show that the AhR is involved in oligodendrocyte level in the formation of the myelin sheath. As the AhR is also a receptor of pollutants, some environmental contaminants may play a role in the incidence of diseases in the central nervous system, which raises many issues in terms of public health.

Thesis (MTech (Chemistry))--Cape Peninsula University of Technology, 2016. / Polycyclic aromatic hydrocarbons (PAHs) are an alarming group of organic substances for humans and environmental organisms due to their ubiquitous presence, toxicity, and carcinogenicity. They are semi-volatile substances which result from the fusion of carbon and hydrogen atoms and constitute a large group of compounds containing two to several aromatic rings in their molecule. Natural processes and several anthropogenic activities involving complete or incomplete combustion of organic substances such as coal, fossil fuel, tobacco and other thermal processes, generally result in the release of the PAHs into the environment. However, the fate of the PAHs is of great environmental concern due to their tendency to accumulate and their persistence in different environmental matrices and their toxicity. Animal studies have revealed that an excessive exposure to PAHs can be harmful. Evidence of their carcinogenic, mutagenic, and immune-suppressive effects has been reported in the literature. In the soil environment, they have the tendency to be absorbed by plants grown on soil being contaminated by the PAHs. It is, therefore, important to evaluate their occurrence levels in different environmental matrices such as soil concentrations.

Introdução: A artrite reumatóide (AR) é uma artropatia autoimune, de caráter inflamatório, com prevalência em torno de 1% da população. O tabagismo é considerado o principal fator de risco para o desenvolvimento da AR. O receptor de hidrocarbonetos de arila (AhR), um fator de transcrição intracelular ativado por hidrocarbonetos aromáticos componentes da fumaça do cigarro, foi identificado como alvo de regulação da diferenciação de células Th17. Objetivos: Avaliar se os polimorfismos genéticos do AhR estariam associados ao desenvolvimento da AR , e se este receptor estaria mais expresso em pacientes com AR. Pacientes e Métodos: Nós analisamos sete polimorfismos genéticos por mudança de única base (SNP) por PCR em tempo real utilizando sondas TaqMan em 138 pacientes com AR e 129 indivíduos saudáveis. A quantificação da expressão do mRNA do AhR em células mononucleares isoladas de pacientes com AR e indivíduos saudáveis foi realizada por PCR em tempo real. Resultados: Identificamos que haplótipos formados por SNPs no AhR estariam associados com desenvolvimento da AR, podendo ser fator protetor ou de risco para a doença. Em adição, os pacientes com haplótipos de risco apresentavam doença com índice de atividade elevado, principalmente quando o tabagismo estava presente. De fato, pacientes com AR apresentaram aumento na expressão de AhR (mRNA) em relação a indivíduos saudáveis. Conclusões: Em conjunto estes resultados sugerem que o AhR possui um papel importante para o desenvolvimento da artrite reumatóide. Possivelmente mutações neste receptor podem estar relacionadas com alterações na sua atividade e conseqüentemente na diferenciação de células Th17 e a susceptibilidade a AR. / Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune arthropaty with inflammatory characteristics and prevalence around 1% in the population. Tabagism is the main risk factor to RA development. The aryl hydrocarbon receptor (AhR) is an intracellular transcription factor activated by aromatic hydrocarbons present in smoking, whichwas identified to be a target of regulation of Th17 differentiation. Purpose: Study the relationship of genetic polymorphisms in AhR with RA development, and if this receptor expression is upregulated in RA patients. Patients and Methods: We analyzed seven genetic single nucleotide polymorphisms by Real-Time PCR using TaqMan probes in 138 patients with Rheumatoid Arthritis and 129 healthy controls. The AhR mRNA quantization in mononuclear cells isolated from AR patients and healthy controls has been done by Realt-Time PCR. Results: We identified that AhR haplotypes were associated with RA development and that they could be protector or risk factors to disease. In addition, patients with risk haplotypes showed higher disease activity index, mainly when smoking was present. Indeed, patients with RA showed upregulation in the AhR expression (mRNA) when compared with healthy controls. Conclusions: These results suggest that AhR has an important role in AR development. Probably, mutations in this receptor could be related with alterations in its activity and consequently in the differentiation of Th17 cells and RA susceptibility.