Article
Gastroenterology & Hepatology
Morgane Modoux, Nathalie Rolhion, Jeremie H. Lefevre, Cyriane Oeuvray, Petr Nadvornik, Peter Illes, Patrick Emond, Yann Parc, Sridhar Mani, Zdenek Dvorak, Harry Sokol
Summary: This study investigated the effect of gut microbiota-derived metabolites on the activation of AhR. It was found that short-chain fatty acids, specifically butyrate, enhance AhR activity without binding to the receptor. Butyrate acts directly on the promoter of AhR target genes through iHDAC activity, reshaping chromatin. These findings provide novel insights into the complex regulation of AhR activation by gut microbiota-derived metabolites.
Article
Immunology
Angela Rico de Souza, Hussein Traboulsi, Xinyu Wang, Jorg H. Fritz, David H. Eidelman, Carolyn J. Baglole
Summary: Research suggests that inhibiting AhR will enhance cigarette smoke-induced pulmonary neutrophilia, but the mechanism of AhR's anti-inflammatory function remains unclear. Through the use of AhR antagonists and genetically modified mice, the study shows that features such as nuclear translocation and binding of response elements are not necessary for AhR to suppress pulmonary neutrophilia.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Toxicology
Ali Ghaffarian-Bahraman, Mohammad-Reza Arabnezhad, Majid Keshavarzi, Dorna Davani-Davari, Akram Jamshidzadeh, Afshin Mohammadi-Bardbori
Summary: The study found that oxidative imbalance induced by AhR ligands (such as FICZ or B alpha P) can affect melanin production by enhancing the expression of melanogenesis-related genes and increasing tyrosinase enzyme activity, leading to oxidative stress. NAC and DPI can enhance melanogenesis by reducing ROS levels, highlighting the critical role of cellular redox status in AhR ligand-induced melanogenesis.
TOXICOLOGY IN VITRO
(2022)
Article
Immunology
Francesca Alessandrini, Renske de Jong, Maria Wimmer, Ann-Marie Maier, Isis Fernandez, Miriam Hils, Jeroen T. Buters, Tilo Biedermann, Ulrich M. Zissler, Christian Hoffmann, Julia Esser-von-Bieren, Carsten B. Schmidt-Weber, Caspar Ohnmacht
Summary: The study shows that the environmental sensor AhR and its downstream target CYP1B1 play an important role in preventing exacerbation of allergic airway inflammation by regulating the expression and signaling in lung epithelial cells. Differential expression and signaling of CYP1 family members via AhR in epithelial cells represent an immunoregulatory layer protecting the lung from exacerbation of allergic airway inflammation.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Thomas E. Zapadka, Sarah I. Lindstrom, Julia C. Batoki, Chieh A. Lee, Brooklyn E. Taylor, Scott J. Howell, Patricia R. Taylor
Summary: The study examined the efficacy of an AhR agonist, VAF347, as a potential therapeutic for non-proliferative diabetic retinopathy. It was found that the AhR agonist significantly reduced leukostasis, oxidative stress, and inflammation in the retina of diabetic mice, and ameliorated retinal capillary degeneration. These findings suggest that VAF347 could be a potentially novel therapeutic for non-proliferative diabetic retinopathy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Kuo-Liang Wei, Guan-Lun Gao, Yu-Ting Chou, Chih-Yi Lin, Shan-Chun Chen, Yi-Ling Chen, Hui Qin Choi, Chi-Chia Cheng, Jyan-Gwo Joseph Su
Summary: This study demonstrates that sorafenib is a potent AhR antagonist, which can effectively suppress the growth of hepatocellular carcinoma and other cancers.
Article
Biochemistry & Molecular Biology
Atefeh Sadeghi Shermeh, Dmytro Royzman, Christine Kuhnt, Christina Drassner, Lena Stich, Alexander Steinkasserer, Ilka Knippertz, Andreas B. Wild
Summary: The different classes of AhR ligands have varying effects on the phenotype and function of hMoDCs. BP induces a tolerogenic response in mature DCs, while this effect is not observed to the same extent with FICZ or I3S. These findings highlight the differential contribution of AhR ligands to DC responses and suggest the need for further studies to understand the underlying mechanisms and molecules involved.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Hamidreza Mohammadi, Gholamreza Daryabor, Ali Ghaffarian Bahraman, Majid Keshavarzi, Kurosh Kalantar, Afshin Mohammadi-Bardbori
Summary: Maintaining redox homeostasis is crucial for cell survival and functionality, as redox imbalance can lead to various pathological states. The engagement of AhR during redox alteration may influence the fate of CD4+ T cells, making AhR agonists or antagonists potentially useful in assessing immune responses. Further verification in vitro and in animal models of different diseases is needed to confirm these results.
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Gang Cao, Hua Miao, Yan-Ni Wang, Dan-Qian Chen, Xia-Qing Wu, Lin Chen, Yan Guo, Liang Zou, Nosratola D. Vaziri, Ping Li, Ying-Yong Zhao
Summary: This study found that the metabolite 1-methoxypyrene (MP) activates the aryl hydrocarbon receptor (AhR) signaling pathway, leading to tubulointerstitial fibrosis (TIF). MP promotes the epithelial-mesenchymal transition and macrophage-myofibroblast transition, which are important for the development of TIF.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Biochemistry & Molecular Biology
Vanessa Brinkmann, Margherita Romeo, Lucie Larigot, Anne Hemmers, Lisa Tschage, Jennifer Kleinjohann, Alfonso Schiavi, Swantje Steinwachs, Charlotte Esser, Ralph Menzel, Sara Giani Tagliabue, Laura Bonati, Fiona Cox, Niloofar Ale-Agha, Philipp Jakobs, Joachim Altschmied, Judith Haendeler, Xavier Coumoul, Natascia Ventura
Summary: The aryl hydrocarbon receptor (AhR) and Nrf2/SKN-1 pathway play important roles in mediating the anti-aging effects of curcumin. Curcumin can extend lifespan through AhR-dependent mechanism in Caenorhabditis elegans, but it also exhibits AhR-independent anti-aging activities. These findings provide insights into the mechanisms of curcumin's effects on aging.
Article
Clinical Neurology
Thanos Tsaktanis, Tobias Beyer, Lucy Nirschl, Mathias Linnerbauer, Verena Grummel, Mathias Bussas, Emily Tjon, Mark Muhlau, Thomas Korn, Bernhard Hemmer, Francisco J. Quintana, Veit Rothhammer
Summary: The study found that AHR ligand levels were decreased in RRMS and correlated with disease duration and neurological disability. In SPMS and PPMS, serum AHR agonistic activity was also decreased and correlated with disease severity. Longitudinally, decreased AHR agonistic activity in RRMS patients was linked to progressive CNS atrophy and increased lesion load, suggesting it could serve as a novel biomarker for disability progression in MS.
NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION
(2021)
Article
Biochemistry & Molecular Biology
Maria Tamayo, Laura Martin-Nunes, Maria Jose Piedras, Maria Martin-Calvo, Daniel Marti-Morente, Marta Gil-Fernandez, Nieves Gomez-Hurtado, Maria Angeles Moro, Lisardo Bosca, Maria Fernandez-Velasco, Carmen Delgado
Summary: This study investigated the effect of AhR signaling on adverse ventricular remodeling in the injured heart. Activation of AhR by FICZ improved cardiac function, attenuated cardiac hypertrophy, and exerted protective effects through multiple pathways, including inhibition of hypertrophic signaling, transcriptional reduction in pro-fibrotic genes, and antioxidant effects mediated by NRF2/NQO1 pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Agriculture, Multidisciplinary
Mu-Zi Li, Yi Zhao, Hao-Ran Wang, Milton Talukder, Jin-Long Li
Summary: In this study, it was found that lycopene (LYC) can significantly alleviate DEHP-induced nephrotoxicity in mice by mediating the AhR/Arnt signaling system, thereby preventing kidney injury.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Xiaoting Xu, Xi Zhang, Yuzhu Yuan, Yongrui Zhao, Hamza M. Fares, Mengjiao Yang, Qing Wen, Reham Taha, Lixin Sun
Summary: This review systematically discusses the species differences in AhR activation effects and their modes of action, focusing on molecular configuration and activation of AhR, as well as comparison of cis-acting elements corresponding to AhR. The variations in responses seen in humans and other species following AhR activation can be attributed to both factors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Fangyi Shi, Noof Aloufi, Hussein Traboulsi, Jean-Francois Trempe, David H. Eidelman, Carolyn J. Baglole
Summary: The study revealed that AhR deficiency increases basal Akt kinase phosphorylation in mouse lung fibroblasts but does not affect Akt phosphorylation under growth factor or AhR ligand stimulation. Furthermore, AhR may modulate the phosphorylation of various novel proteins, influencing cell survival and function through unknown mechanisms.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Afsaneh Ghaedi, Majid Keshavarzi, Ali Ghafarian Bahraman, Afshin Mohammadi-Bardbori
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
(2020)
Article
Pharmacology & Pharmacy
Ali Ghaffarian Bahraman, Akram Jamshidzadeh, Majid Keshavarzi, Mohammad-Reza Arabnezhad, Hamidreza Mohammadi, Afshin Mohammadi-Bardbori
Summary: This study investigated the regulatory role of AhR in alpha-MSH-induced melanogenesis. The results showed that AhR plays a role in regulating melanogenesis stimulated by alpha-MSH, with changes in gene expression, tyrosinase activity, and melanin content observed.
INTERNATIONAL JOURNAL OF TOXICOLOGY
(2021)
Review
Gastroenterology & Hepatology
Brigitta Stockinger, Kathleen Shah, Emma Wincent
Summary: The Aryl hydrocarbon receptor (AHR) signaling pathway plays significant roles in the intestine, regulating various cell types and impacting inflammation and tumorigenesis. AHR is a ligand-dependent transcription factor that translocates to the nucleus upon ligand binding, where it interacts with other proteins to modulate gene expression. Research has shown that AHR not only responds to environmental pollutants, but also serves important beneficial functions in immune, epithelial, endothelial, and neuronal cells within the intestinal microenvironment.
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Hamidreza Mohammadi, Gholamreza Daryabor, Ali Ghaffarian Bahraman, Majid Keshavarzi, Kurosh Kalantar, Afshin Mohammadi-Bardbori
Summary: Maintaining redox homeostasis is crucial for cell survival and functionality, as redox imbalance can lead to various pathological states. The engagement of AhR during redox alteration may influence the fate of CD4+ T cells, making AhR agonists or antagonists potentially useful in assessing immune responses. Further verification in vitro and in animal models of different diseases is needed to confirm these results.
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
(2021)
Article
Cell Biology
Oscar E. Diaz, Chiara Sorini, Rodrigo A. Morales, Xinxin Luo, Annika Frede, Annette M. Krais, Myra N. Chavez, Emma Wincent, Srustidhar Das, Eduardo J. Villablanca
Summary: The study revealed that PFOS exacerbates inflammation-induced intestinal damage, disrupts T-cell homeostasis, and provides a novel in vivo toolbox for screening pollutants affecting intestinal homeostasis.
DISEASE MODELS & MECHANISMS
(2021)
Editorial Material
Dermatology
John Ulf Rannug
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Article
Microbiology
Rehab El-Shehawy, Sandra Luecke-Johansson, Anton Ribbenstedt, Elena Gorokhove
Summary: This study revealed a peripheral catecholamine pathway involving the gut microbiome of Daphnia magna, highlighting the role of L-Dopa in communication between the host and microbiome. The findings suggest a crucial role of L-Dopa in the bidirectional communication between the animal host and its gut bacteria, influencing ecologically important host traits.
Article
Marine & Freshwater Biology
Andreas N. M. Eriksson, Cyril Rigaud, Aleksei Krasnov, Emma Wincent, Eeva-Riikka Vehniainen
Summary: This study investigates the cardiotoxicity mechanisms of different PAHs and their binary mixtures in rainbow trout alevins. The results reveal that different PAHs have unique toxicity profiles, with some causing growth inhibition and heart damage. The toxicity effects are related to PAH body burden and the regulation of specific genes.
AQUATIC TOXICOLOGY
(2022)
Article
Toxicology
Ali Ghaffarian-Bahraman, Mohammad-Reza Arabnezhad, Majid Keshavarzi, Dorna Davani-Davari, Akram Jamshidzadeh, Afshin Mohammadi-Bardbori
Summary: The study found that oxidative imbalance induced by AhR ligands (such as FICZ or B alpha P) can affect melanin production by enhancing the expression of melanogenesis-related genes and increasing tyrosinase enzyme activity, leading to oxidative stress. NAC and DPI can enhance melanogenesis by reducing ROS levels, highlighting the critical role of cellular redox status in AhR ligand-induced melanogenesis.
TOXICOLOGY IN VITRO
(2022)
Article
Ecology
Andreas N. M. Eriksson, Cyril Rigaud, Emma Wincent, Hannu Pakkanen, Pihla Salonen, Eeva-Riikka Vehniainen
Summary: Multiple studies have shown that PAH mixtures have a synergized toxicity in developing fish larvae. The accumulation of endogenous metabolites, such as FICZ, may contribute to this synergistic effect.
Article
Environmental Sciences
Burcu Unlu Endirlik, Emma Wincent, Kristian Dreij
Summary: This study investigated the effects of binary mixtures of polycyclic aromatic hydrocarbons (PAHs) and pesticides on human liver cells (HepG2) and zebrafish embryos. The results showed that these mixtures had different interactions on cell viability and gene expression, and caused developmental defects in zebrafish embryos. Moreover, the study found that the activation of aryl hydrocarbon receptor (AhR) and inhibition of cytochrome P4501a1 (CYP1A1) were responsible for the non-additive interaction between PAHs and pesticides.
ENVIRONMENTAL POLLUTION
(2023)
Article
Chemistry, Medicinal
Maryam Jamil, Afshin Mohammadi-Bardbori, Omid Safa, Amin Reza Nikpoor, Azizollah Bakhtari, Mahnoosh Mokhtarinejad, Saghar Naybandi Zadeh, Amir Shadboorestan, Mahmoud Omidi
Summary: Lung cancer is a highly deadly cancer globally, and arsenic trioxide (ATO) is still an effective drug for treating acute promyelocytic leukemia (APL). Chemotherapy resistance is a major issue in cancer therapy, but necroptosis has the potential to overcome this resistance and promote cancer treatment. This study examines the necroptosis pathway in A549 cancer cells exposed to ATO.
Article
Toxicology
Majid Keshavarzi, Fatemeh Moradbeygi, Keivan Mobini, Ali Ghaffarian Bahraman, Parisa Mohammadi, Afsaneh Ghaedi, Afshin Mohammadi-Bardbori
Summary: The study found that the endogenous ligand of AhR regulates the APP gene, the interaction between AhR/WNT/CTNNB1 has a positive regulatory effect on APP mRNA and protein expression, while Notch has a negative regulatory effect, which correlates with mice's learning skills and memory.
TOXICOLOGY RESEARCH
(2022)
Article
Environmental Sciences
Cyril Rigaud, Andreas Eriksson, Aleksei Krasnov, Emma Wincent, Hannu Pakkanen, Heli Lehtivuori, Janne Ihalainen, Eeva-Riikka Vehniainen
SCIENCE OF THE TOTAL ENVIRONMENT
(2020)
Article
Cell Biology
Keivan Mobini, Elham Banakar, Gholamhossein Tamaddon, Afshin Mohammadi-Bardbori