5 results on '"Aryl Hydrocarbon Receptor"'
Search Results
2. Study of indoleamine 2,3-dioxygenase in bladder cancer: correlation with clinicopathological parameters, relationship with BCG and its chemical inhibition
- Author
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Matheus, Luiz Henrique Gomes, Dellê, Humberto, Dalboni, Maria Aparecida, Marcos, Rodrigo Labat, and Moreno, Maria Carolina Ramos
- Subjects
receptor de hidrocarboneto de arila ,CIENCIAS DA SAUDE ,aryl hydrocarbon receptor ,BCG ,Indoleamine 2,3-dioxygenase 1 ,Indoleamina 2,3-dioxigenase 1 - Abstract
Submitted by Nadir Basilio (nadirsb@uninove.br) on 2021-11-18T19:44:21Z No. of bitstreams: 1 Luiz Henrique Gomes Matheus.pdf: 2644993 bytes, checksum: b311ff61c9f945e8ba5726083bc80490 (MD5) Made available in DSpace on 2021-11-18T19:44:21Z (GMT). No. of bitstreams: 1 Luiz Henrique Gomes Matheus.pdf: 2644993 bytes, checksum: b311ff61c9f945e8ba5726083bc80490 (MD5) Previous issue date: 2020-03-23 Bladder cancer (BC) has a high rate of recurrence and progression even after TUR associated with BCG immunotherapy. Indoleamine 2,3-dioxigenase 1 (IDO) is an immunomodulatory enzyme implied in the immune escape and progression of several types of cancer, acting through signaling pathways, such as GCN2 (general control nonderepressible 2) and AHR (aryl hydrocarbon receptor). Because it is strongly induced by interferon-gamma, a BCG-induced cytokine, IDO may be responsible for part of the progression of BC after conventional treatment. The inhibition of IDO becomes attractive, but the effect of inhibitors over its pathways in BC is not known. The objectives were: (i) to verify if the IDO is associated with the progression of the BC; (ii) verify whether BCG induces IDO in the BC; and (ii) check if two usual IDO inhibitors interfere with the GNC2 and AHR pathways in the BC. Biopsies from 155 patients with BC were selected for the study, 88 with non-muscle-invasive BC (NMI) and 67 with muscle-invasive BC (MI). Immunohistochemistry for IDO was performed to correlate its expression with clinicopathological data acquired from medical records. The effect of BCG on the expression of IDO was investigated in culture of human lines of BC and in in vivo model, evaluating it by means of immunohistochemistry and real-time PCR. Inhibitors of IDO 1-methyl-D-tryptophan (MT) and INCB024360 (INCB) were evaluated in cell culture and MT in animal model. The inhibition of IDO was measured by measuring L-quinurenine in the supernatant and the activation of the GCN2 and AHR pathways by real-time PCR for CHOP and CYP1A1, respectively. As a result, the expression of IDO correlates positively with the progression of the BC (grade and stage). The use of BCG had no effect on the expression of IDO, either in culture or in animal model. The evaluated inhibitors were effective in inhibiting IDO, but MT induced the AHR pathway triggered by IDO, as an agonist. In conclusion, (i) the IDO has the potential to assist in the prognosis of BC, as it is associated with advanced degree and stage of BC; (ii) BCG does not directly induce the expression of IDO in BC, remaining as a safe adjuvant treatment; (iii) between the two IDO inhibitors evaluated, the INCB is promising, while MT offers risk for activating the AHR pathway, a pathway recognized as a potential for tumor escape and progression. O câncer de bexiga (CB) apresenta alta taxa de recorrência e progressão mesmo após RTU associada à imunoterapia com BCG. A indoleamina 2,3-dioxigenase 1 (IDO) é uma enzima imunomoduladora implicada no escape imunológico e progressão de diversos tipos de câncer, agindo por meio de vias de sinalização, tais como GCN2 (general control nondrepressible 2) e AHR (aryl hydrocarbon receptor). Por ser fortemente induzida por interferon-gama, uma citocina induzida por BCG, a IDO pode ser responsável por parte da progressão do CB após o tratamento convencional. A inibição da IDO torna-se atraente, porém o efeito dos inibidores sobre as suas vias no CB não é conhecido. Os objetivos foram: (i) verificar se a IDO está associada com a progressão do CB; (ii) verificar se o BCG induz IDO no CB; e (ii) verificar se dois inibidores usuais da IDO interferem nas vias GNC2 e AHR no CB. Biópsias de 155 pacientes com CB foram selecionadas para o estudo, sendo 88 com CB não músculo-invasivo (NMI) e 67 com CB músculo-invasivo (MI). Imunohistoquímica para IDO foi realizada para correlacionar sua expressão com os dados clinicopatológicos adquiridos dos prontuários. O efeito do BCG sobre a expressão de IDO foi investigado em cultura de linhagens humanas de CB e em modelo in vivo, avaliando-a por meio de imunohistoquímica e PCR em tempo real. Os inibidores da IDO 1-metil-D-triptofano (MT) e INCB024360 (INCB) foram avaliados em cultura de células e o MT em modelo animal. A inibição da IDO foi aferida pela mensuração de L-quinurenina no sobrenadante e a ativação das vias GCN2 e AHR por meio de PCR em tempo real para CHOP e CYP1A1, respectivamente. Como resultados, a expressão de IDO correlaciona-se positivamente com progressão do CB (grau e estádio). Já o uso de BCG não exerceu efeito sobre a expressão de IDO, tanto em cultura como em modelo animal. Os inibidores avaliados foram eficazes em inibir a IDO, porém o MT induziu a via AHR acionada pela IDO, como um agonista. Como conclusão, (i) a IDO tem potencial para auxiliar no prognóstico do CB, pois associa-se com grau e estagio avançados de CB; (ii) o BCG não induz diretamente a expressão de IDO no CB, mantendo-se como um tratamento adjuvante seguro; (iii) entre os dois inibidores da IDO avaliados, o INCB mostra-se promissor, enquanto o MT oferece risco por acionar a via AHR, uma via reconhecida como potencializadora de escape e progressão tumorais.
- Published
- 2020
3. Unbalanced expression of aryl hydrocarbon receptor in peripheral blood CCR6+CD4+ and CD4+CD25+T cells of rheumatoid arthritis
- Author
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Lin Cheng, Long Qian, Yue Tan, Guo-Sheng Wang, Xiao-Mei Li, Xiang-Pei Li, and Chao-Yin Luo
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Rheumatoid arthritis ,Aryl hydrocarbon receptor ,CD4+CD25+T cells ,CCR6+CD4+T cells ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
ABSTRACT Objective: The goal of this study was to analyze the role of aryl hydrocarbon receptor in peripheral blood CCR6+CD4+ and CD4+CD25+T cells of patients with rheumatoid arthritis. Methods: Flow cytometry was applied to determine the proportion of AhR positive cells in CCR6+CD4+T, CD4+CD25+T and peripheral blood peripheral mononuclear cells from each subject. AhR mRNA and CYP1A1 mRNA relative expression levels were tested by real-time PCR. Results: The percentage of AhR positive cells in peripheral blood mononuclear cells was higher in RA group than that in healthy cases [(35.23 ± 10.71)% vs. (18.83 ± 7.32)%, p < 0.01]. The expression levels of AhR and CYP1A1 were both increased in patients with RA while compared to controls [(3.71 ± 1.63) vs. (2.00 ± 1.27), p = 0.002; (2.62 ± 2.08) vs. (0.62 ± 0.29), p < 0.01, respectively]. In RA patients, the percentage of AhR positive cells in CD4+CD25+T cells was significantly lower than that from controls [17.90 (6.10 ± 80.10)% vs. (52.49 ± 19.18)%, p < 0.01]; In healthy controls, the percentage of AhR positive cells in CD4+CD25+T cells was significantly higher than that in CCR6+CD4+T cells, and was also significantly higher than that in PBMCs [(52.49 ± 19.18)% vs. (23.18 ± 5.62)% vs. (18.06 ± 7.80)%, X 2 = 24.03, p < 0.01]; in RA patients, the percentage of AhR positive cells in CCR6+CD4+T cells was significantly increased than that in CD4+CD25+T cells and PBMCs [(46.02 ± 14.68)% vs. 17.90 (6.10 ± 80.10)% vs. (34.22 ± 10.33)%, X 2 = 38.29, p < 0.01]; Nevertheless, no statistically significant relationship was found between clinical data and AhR positive cells in CCR6+CD4+T and CD4+CD25+T cells. Conclusion: AhR may participate in the pathological progress of RA by controlling the differentiation of Th17 and Treg cells in peripheral blood.
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4. Resistant starch supplementation effects on plasma indole 3-acetic acid and aryl hydrocarbon receptor mRNA expression in hemodialysis patients: Randomized, double blind and controlled clinical trial
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Renata Azevedo, Marta Esgalhado, Julie Ann Kemp, Bruna Regis, Ludmila FMF Cardozo, Lia S. Nakao, Jessyca Sousa de Brito, and Denise Mafra
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prebiotics ,aryl hydrocarbon receptor ,inflammation ,chronic kidney disease ,hemodialysis ,Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
ABSTRACT Introduction: Gut microbiota imbalance is linked to high uremic toxins production such as indole-3-acetic acid (IAA) in chronic kidney disease patients. This toxin can activate the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor involved with inflammation. Strategies to restore gut microbiota balance can be associated with reduced production of IAA and its deleterious effects. This study aimed to evaluate prebiotic resistant starch (RS) supplementation effects on IAA plasma levels and AhR mRNA expression in CKD patients on hemodialysis (HD). Methods: This randomized, double-blind and placebo-controlled clinical trial evaluated forty-two stable HD patients allocated in RS (n=22) or placebo (n=20) groups. Patients received, alternately, cookies and sachets containing 16 g/day of RS (Hi-Maize 260®) or manioc flour for four weeks. Fasting pre-dialysis blood samples were collected and IAA plasma levels measured by high performance liquid chromatography. Peripheral blood mononuclear cells were isolated and processed for AhR and nuclear factor kappa B (NF-κB) mRNA expression analyzes by quantitative real-time PCR. Anthropometric and biochemical parameters, as well as food intake were also evaluated. Results: Thirty-one patients completed the study, 15 in the RS group and 16 in the placebo group. Although there was no significant alteration in IAA plasma levels, neither in AhR mRNA expression and NF-κB mRNA expression after RS supplementation, a positive correlation (r=0.48; p=0.03) was observed between IAA plasma levels and AhR expression at baseline. Conclusion: Even though prebiotic RS supplementation did not influence IAA levels or AhR expression, their positive association reinforces a possible interaction between them.
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5. Unbalanced expression of aryl hydrocarbon receptor in peripheral blood CCR6 + CD4 + and CD4 + CD25 + T cells of rheumatoid arthritis.
- Author
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Cheng L, Qian L, Tan Y, Wang GS, Li XM, Li XP, and Luo CY
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- Adult, Arthritis, Rheumatoid blood, Biomarkers blood, CD4-Positive T-Lymphocytes metabolism, Case-Control Studies, Female, Flow Cytometry, Humans, Interleukin-2 Receptor alpha Subunit blood, Male, Middle Aged, Real-Time Polymerase Chain Reaction, Receptors, CCR6 blood, Reverse Transcriptase Polymerase Chain Reaction, T-Lymphocytes, Regulatory metabolism, Th17 Cells metabolism, Arthritis, Rheumatoid immunology, Basic Helix-Loop-Helix Transcription Factors blood, Receptors, Aryl Hydrocarbon blood, T-Lymphocytes metabolism
- Abstract
Objective: The goal of this study was to analyze the role of aryl hydrocarbon receptor in peripheral blood CCR6
+ CD4+ and CD4+ CD25+ T cells of patients with rheumatoid arthritis., Methods: Flow cytometry was applied to determine the proportion of AhR positive cells in CCR6+ CD4+ T, CD4+ CD25+ T and peripheral blood peripheral mononuclear cells from each subject. AhR mRNA and CYP1A1 mRNA relative expression levels were tested by real-time PCR., Results: The percentage of AhR positive cells in peripheral blood mononuclear cells was higher in RA group than that in healthy cases [(35.23±10.71)% vs. (18.83±7.32)%, p<0.01]. The expression levels of AhR and CYP1A1 were both increased in patients with RA while compared to controls [(3.71±1.63) vs. (2.00±1.27), p=0.002; (2.62±2.08) vs. (0.62±0.29), p<0.01, respectively]. In RA patients, the percentage of AhR positive cells in CD4+ CD25+ T cells was significantly lower than that from controls [17.90 (6.10±80.10)% vs. (52.49±19.18)%, p<0.01]; In healthy controls, the percentage of AhR positive cells in CD4+ CD25+ T cells was significantly higher than that in CCR6+ CD4+ T cells, and was also significantly higher than that in PBMCs [(52.49±19.18)% vs. (23.18±5.62)% vs. (18.06±7.80)%, X2 =24.03, p<0.01]; in RA patients, the percentage of AhR positive cells in CCR6+ CD4+ T cells was significantly increased than that in CD4+ CD25+ T cells and PBMCs [(46.02±14.68)% vs. 17.90 (6.10±80.10)% vs. (34.22±10.33)%, X2 =38.29, p<0.01]; Nevertheless, no statistically significant relationship was found between clinical data and AhR positive cells in CCR6+ CD4+ T and CD4+ CD25+ T cells., Conclusion: AhR may participate in the pathological progress of RA by controlling the differentiation of Th17 and Treg cells in peripheral blood., (Copyright © 2016 Elsevier Editora Ltda. All rights reserved.)- Published
- 2017
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