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Implications of xenobiotic-response element(s) and aryl hydrocarbon receptor in health and diseases

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Abstract

The effect of air pollution on public health is severely detrimental. In humans; the physiological response against pollutants is mainly elicited via the activation of aryl hydrocarbon receptor (AhR). It acts as a prime sensor of xenobiotic chemicals, also functioning as a transcription factor regulating a variety of gene expressions. Along with AhR, another pivotal element of the pollution stress pathway is Xenobiotic Response Elements (XREs). XRE, as studied are some conserved sequences in the DNA, responsible for the physiological response against pollutants. XRE is present at the upstream of the inducible target genes of AhR and it regulates the function of the AhR. XRE(s) are highly conserved in species as it has only eight specific sequences found so far in humans, mice, and rats. Inhalation of toxicants like dioxins, gaseous industrial effluents, and smoke from burning fuel and tobacco leads to predominant damage to the lungs. However, scientists are exploring the involvement of AhR in chronic diseases for example chronic obstructive pulmonary disease (COPD) and also other lethal diseases like lung cancer. In this review, we summarise what is known at this time about the roles played by the XRE and AhR in our molecular systems that have a defined control in the normal maintenance of homeostasis as well as dysfunctions.

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References

  1. Li S, Pei X, Zhang W, Xie HQ, Zhao B. Functional analysis of the dioxin response elements (DREs) of the murine CYP1A1 gene promoter: beyond the core DRE sequence. Int J Mol Sci. 2014;15(4):6475–87. https://doi.org/10.3390/ijms15046475.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Phelan D, Winter GM, Rogers WJ, Lam JC, Denison MS. Activation of the Ah receptor signal transduction pathway by bilirubin and biliverdin. Arch Biochem Biophys. 1998;357(1):155–63. https://doi.org/10.1006/abbi.1998.0814.

    Article  CAS  PubMed  Google Scholar 

  3. Denison MS, Pandini A, Nagy SR, Baldwin EP, Bonati L. Ligand binding and activation of the Ah receptor. Chem Biol Interact. 2002;141(1–2):3–24. https://doi.org/10.1016/s0009-2797(02)00063-7.

    Article  CAS  PubMed  Google Scholar 

  4. Ma Q, Whitlock JP. A Novel cytoplasmic protein that interacts with the Ah receptor, contains tetratricopeptide repeat motifs, and augments the transcriptional response to 2,3,7,8-tetrachlorodibenzo-p-dioxin*. J Biol Chem. 1997;272(14):8878–84. https://doi.org/10.1074/jbc.272.14.8878.

    Article  CAS  PubMed  Google Scholar 

  5. Meyer BK, Pray-Grant MG, Vanden Heuvel JP, Perdew GH. Hepatitis B virus X-associated protein 2 is a subunit of the unliganded aryl hydrocarbon receptor core complex and exhibits transcriptional enhancer activity. Mol Cell Biol. 1998;18(2):978–88. https://doi.org/10.1128/MCB.18.2.978.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Hord NG, Perdew GH. Physicochemical and immunocytochemical analysis of the aryl hydrocarbon receptor nuclear translocator: characterization of two monoclonal antibodies to the aryl hydrocarbon receptor nuclear translocator. Mol Pharmacol. 1994;46(4):618–26.

    CAS  PubMed  Google Scholar 

  7. Pollenz RS, Sattler CA, Poland A. The aryl hydrocarbon receptor and aryl hydrocarbon receptor nuclear translocator protein show distinct subcellular localizations in Hepa 1c1c7 cells by immunofluorescence microscopy. Mol Pharmacol. 1994;45(3):428–38.

    CAS  PubMed  Google Scholar 

  8. Probst MR, Reisz-Porszasz S, Agbunag RV, Ong MS, Hankinson O. Role of the aryl hydrocarbon receptor nuclear translocator protein in aryl hydrocarbon (dioxin) receptor action. Mol Pharmacol. 1993;44(3):511–8.

    CAS  PubMed  Google Scholar 

  9. Bank PA, Yao EF, Phelps CL, Harper PA, Denison MS. Species-specific binding of transformed Ah receptor to a dioxin responsive transcriptional enhancer. Eur J Pharmacol. 1992;228(2–3):85–94. https://doi.org/10.1016/0926-6917(92)90016-6.

    Article  CAS  PubMed  Google Scholar 

  10. Ma Q. Induction of CYP1A1. The AhR/DRE paradigm: transcription, receptor regulation, and expanding biological roles. Curr Drug Metab. 2001;2(2):149–64. https://doi.org/10.2174/1389200013338603.

    Article  CAS  PubMed  Google Scholar 

  11. Shen ES, Whitlock JP Jr. The potential role of DNA methylation in the response to 2,3,7,8-tetrachlorodibenzo-<em>p</em>-dioxin *. J Biol Chem. 1989;264(30):17754–8. https://doi.org/10.1016/S0021-9258(19)84636-7.

    Article  CAS  PubMed  Google Scholar 

  12. Henry EC, Rucci G, Gasiewicz TA. Characterization of multiple forms of the Ah receptor: comparison of species and tissues. Biochemistry. 1989;28(15):6430–40. https://doi.org/10.1021/bi00441a041.

    Article  CAS  PubMed  Google Scholar 

  13. Jones KW, Whitlock JPJ. Functional analysis of the transcriptional promoter for the CYP1A1 gene. Mol Cell Biol. 1990;10(10):5098–105. https://doi.org/10.1128/mcb.10.10.5098-5105.1990.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Jones PB, Durrin LK, Fisher JM, Whitlock JPJ. Control of gene expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Multiple dioxin-responsive domains 5’-ward of the cytochrome P1–450 gene. J Biol Chem. 1986;261(15):6647–50.

    Article  CAS  PubMed  Google Scholar 

  15. Jones PB, Durrin LK, Galeazzi DR, Whitlock JPJ. Control of cytochrome P1–450 gene expression: analysis of a dioxin-responsive enhancer system. Proc Natl Acad Sci USA. 1986;83(9):2802–6. https://doi.org/10.1073/pnas.83.9.2802.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Denison MS, Fisher JM, Whitlock JPJ. Inducible, receptor-dependent protein-DNA interactions at a dioxin-responsive transcriptional enhancer. Proc Natl Acad Sci USA. 1988;85(8):2528–32. https://doi.org/10.1073/pnas.85.8.2528.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Fisher JM, Wu L, Denison MS, Whitlock JPJ. Organization and function of a dioxin-responsive enhancer. J Biol Chem. 1990;265(17):9676–81.

    Article  CAS  PubMed  Google Scholar 

  18. Kolluri SK, Jin U-H, Safe S. Role of the aryl hydrocarbon receptor in carcinogenesis and potential as an anti-cancer drug target. Arch Toxicol. 2017;91(7):2497–513. https://doi.org/10.1007/s00204-017-1981-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. “Tissue expression of AHR - Summary - The Human Protein Atlas.” https://www.proteinatlas.org/ENSG00000106546-AHR/tissue. Accessed 12 Jan 2023

  20. Chiba T, Uchi H, Yasukawa F, Furue M. Role of the arylhydrocarbon receptor in lung disease. Int Arch Allergy Immunol. 2011;155(Suppl):129–34. https://doi.org/10.1159/000327499.

    Article  CAS  PubMed  Google Scholar 

  21. Kawajiri K, Fujii-Kuriyama Y. The aryl hydrocarbon receptor: a multifunctional chemical sensor for host defense and homeostatic maintenance. Exp Anim. 2017;66(2):75–89. https://doi.org/10.1538/expanim.16-0092.

    Article  CAS  PubMed  Google Scholar 

  22. Wang GL, Semenza GL. Purification and characterization of hypoxia-inducible factor 1. J Biol Chem. 1995;270(3):1230–7. https://doi.org/10.1074/jbc.270.3.1230.

    Article  CAS  PubMed  Google Scholar 

  23. Poland A, Knutson JC. 2,3,7,8-tetrachlorodibenzo-p-dioxin and related halogenated aromatic hydrocarbons: examination of the mechanism of toxicity. Annu Rev Pharmacol Toxicol. 1982;22:517–54. https://doi.org/10.1146/annurev.pa.22.040182.002505.

    Article  CAS  PubMed  Google Scholar 

  24. Kozak KR, Abbott B, Hankinson O. ARNT-deficient mice and placental differentiation. Dev Biol. 1997;191(2):297–305. https://doi.org/10.1006/dbio.1997.8758.

    Article  CAS  PubMed  Google Scholar 

  25. Haarmann-Stemmann T, Abel J. The arylhydrocarbon receptor repressor (AhRR): structure, expression, and function. Biol Chem. 2006;387(9):1195–9. https://doi.org/10.1515/BC.2006.147.

    Article  CAS  PubMed  Google Scholar 

  26. Chiba T, Uchi H, Tsuji G, Gondo H, Moroi Y, Furue M. Arylhydrocarbon receptor (AhR) activation in airway epithelial cells induces MUC5AC via reactive oxygen species (ROS) production. Pulm Pharmacol Ther. 2011;24(1):133–40. https://doi.org/10.1016/j.pupt.2010.08.002.

    Article  CAS  PubMed  Google Scholar 

  27. Quintana FJ, et al. Control of T(reg) and T(H)17 cell differentiation by the aryl hydrocarbon receptor. Nature. 2008;453(7191):65–71. https://doi.org/10.1038/nature06880.

    Article  CAS  PubMed  Google Scholar 

  28. Fujisawa-Sehara A, Sogawa K, Nishi C, Fujii-Kuriyama Y. Regulatory DNA elements localized remotely upstream from the drug-metabolizing cytochrome P-450c gene. Nucleic Acids Res. 1986;14(3):1465–77. https://doi.org/10.1093/nar/14.3.1465.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Denison MS, Fisher JM, Whitlock JPJ. The DNA recognition site for the dioxin-Ah receptor complex. Nucleotide sequence and functional analysis. J Biol Chem. 1988;263(33):17221–4.

    Article  CAS  PubMed  Google Scholar 

  30. Rushmore TH, Pickett CB. Transcriptional regulation of the rat glutathione S-transferase Ya subunit gene. Characterization of a xenobiotic-responsive element controlling inducible expression by phenolic antioxidants. J Biol Chem. 1990;265(24):14648–53.

    Article  CAS  PubMed  Google Scholar 

  31. Favreau LV, Pickett CB. Transcriptional regulation of the rat NAD(P)H:quinone reductase gene. Characterization of a DNA-protein interaction at the antioxidant responsive element and induction by 12-O-tetradecanoylphorbol 13-acetate. J Biol Chem. 1993;268(26):19875–81.

    Article  CAS  PubMed  Google Scholar 

  32. Fujisawa-Sehara A, Yamane M, Fujii-Kuriyama Y. A DNA-binding factor specific for xenobiotic responsive elements of P-450c gene exists as a cryptic form in cytoplasm: its possible translocation to nucleus. Proc Natl Acad Sci USA. 1988;85(16):5859–63. https://doi.org/10.1073/pnas.85.16.5859.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Yamamoto K, Nakano M, Ishihama A. Regulatory role of transcription factor SutR (YdcN) in sulfur utilization in Escherichia coli. Microbiology. 2015;161(Pt 1):99–111. https://doi.org/10.1099/mic.0.083550-0.

    Article  CAS  PubMed  Google Scholar 

  34. Julian T, Michel R, Victor S, Ina A, Sylvie E. Transcription inhibitors with XRE DNA-binding and cupin signal-sensing domains drive metabolic diversification in pseudomonas. mSystems. 2021;6(1):e00753-e820. https://doi.org/10.1128/mSystems.00753-20.

    Article  Google Scholar 

  35. Kiely PD, J. O&apos;Callaghan, Abbas A, F. O&apos;Gara. Genetic analysis of genes involved in dipeptide metabolism and cytotoxicity in Pseudomonas aeruginosa PAO1. Microbiology. 2008;154(8):2209–18. https://doi.org/10.1099/mic.0.2007/015032-0.

    Article  CAS  PubMed  Google Scholar 

  36. Jackson DP, Joshi AD, Elferink CJ. Ah receptor pathway intricacies; signaling through diverse protein partners and DNA-motifs. Toxicol Res (Camb). 2015;4(5):1143–58. https://doi.org/10.1039/c4tx00236a.

    Article  CAS  PubMed  Google Scholar 

  37. Panteleyev AA, Bickers DR. Dioxin-induced chloracne—reconstructing the cellular and molecular mechanisms of a classic environmental disease. Exp Dermatol. 2006;15(9):705–30. https://doi.org/10.1111/J.1600-0625.2006.00476.X.

    Article  CAS  PubMed  Google Scholar 

  38. Ciolino HP, Daschner PJ, Yeh GC. Dietary flavonols quercetin and kaempferol are ligands of the aryl hydrocarbon receptor that affect CYP1A1 transcription differentially. Biochem J. 1999;340(Pt 3):715–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Beischlag TV, et al. Recruitment of the NCoA/SRC-1/p160 family of transcriptional coactivators by the aryl hydrocarbon receptor/aryl hydrocarbon receptor nuclear translocator complex. Mol Cell Biol. 2002;22(12):4319–33. https://doi.org/10.1128/MCB.22.12.4319-4333.2002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Davarinos NA, Pollenz RS. Aryl hydrocarbon receptor imported into the nucleus following ligand binding is rapidly degraded via the cytosplasmic proteasome following nuclear export. J Biol Chem. 1999;274(40):28708–15. https://doi.org/10.1074/jbc.274.40.28708.

    Article  CAS  PubMed  Google Scholar 

  41. Xing X, et al. SUMOylation of AhR modulates its activity and stability through inhibiting its ubiquitination. J Cell Physiol. 2012;227(12):3812–9. https://doi.org/10.1002/jcp.24092.

    Article  CAS  PubMed  Google Scholar 

  42. Knerr S, Schrenk D. Carcinogenicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in experimental models. Mol Nutr Food Res. 2006;50(10):897–907. https://doi.org/10.1002/mnfr.200600006.

    Article  CAS  PubMed  Google Scholar 

  43. Dietrich C, Kaina B. The aryl hydrocarbon receptor (AhR) in the regulation of cell-cell contact and tumor growth. Carcinogenesis. 2010;31(8):1319–28. https://doi.org/10.1093/carcin/bgq028.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Shimizu Y, et al. Benzo[a]pyrene carcinogenicity is lost in mice lacking the aryl hydrocarbon receptor. Proc Natl Acad Sci USA. 2000;97(2):779–82. https://doi.org/10.1073/pnas.97.2.779.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Shi S, et al. The aryl hydrocarbon receptor nuclear translocator (Arnt) is required for tumor initiation by benzo[a]pyrene. Carcinogenesis. 2009;30(11):1957–61. https://doi.org/10.1093/CARCIN/BGP201.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Thum T, Erpenbeck VJ, Moeller J, Hohlfeld JM, Krug N, Borlak J. Expression of xenobiotic metabolizing enzymes in different lung compartments of smokers and nonsmokers. Environ Health Perspect. 2006;114(11):1655–61. https://doi.org/10.1289/ehp.8861.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Kim JH, Sherman ME, Curriero FC, Guengerich FP, Strickland PT, Sutter TR. Expression of cytochromes P450 1A1 and 1B1 in human lung from smokers, non-smokers, and ex-smokers. Toxicol Appl Pharmacol. 2004;199(3):210–9. https://doi.org/10.1016/j.taap.2003.11.015.

    Article  CAS  PubMed  Google Scholar 

  48. Matsumoto Y, et al. Aryl hydrocarbon receptor plays a significant role in mediating airborne particulate-induced carcinogenesis in mice. Environ Sci Technol. 2009;41(10):3775–80. https://doi.org/10.1021/ES062793G.

    Article  Google Scholar 

  49. McLemore TL, et al. Expression of CYP1A1 gene in patients with lung cancer: evidence for cigarette smoke-induced gene expression in normal lung tissue and for altered gene regulation in primary pulmonary carcinomas. J Natl Cancer Inst. 1990;82(16):1333–9. https://doi.org/10.1093/jnci/82.16.1333.

    Article  CAS  PubMed  Google Scholar 

  50. Oyama T, et al. Cytochrome P450 expression (CYP) in non-small cell lung cancer. Front Biosci. 2007;12:2299–308. https://doi.org/10.2741/2232.

    Article  CAS  PubMed  Google Scholar 

  51. Lin P, Chang H, Ho WL, Wu M-H, Su J-M. Association of aryl hydrocarbon receptor and cytochrome P4501B1 expressions in human non-small cell lung cancers. Lung Cancer. 2003;42(3):255–61. https://doi.org/10.1016/s0169-5002(03)00359-3.

    Article  PubMed  Google Scholar 

  52. Nerurkar PV, et al. Ahr locus phenotype in congenic mice influences hepatic and pulmonary DNA adduct levels of 2-amino-3-methylimidazo[4,5-f]quinoline in the absence of cytochrome P450 induction. Mol Pharmacol. 1996;49(5):874–81.

    CAS  PubMed  Google Scholar 

  53. Nerurkar PV, et al. DNA adducts of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in colon, bladder, and kidney of congenic mice differing in Ah responsiveness and N-acetyltransferase genotype. Cancer Res. 1995;55(14):3043–9.

    CAS  PubMed  Google Scholar 

  54. Revel A, et al. Resveratrol, a natural aryl hydrocarbon receptor antagonist, protects lung from DNA damage and apoptosis caused by benzo[a]pyrene. J Appl Toxicol. 2003;23(4):255–61. https://doi.org/10.1002/jat.916.

    Article  CAS  PubMed  Google Scholar 

  55. Sagredo C, Øvrebø S, Haugen A, Fujii-Kuriyama Y, Baera R, Botnen IV, Mollerup S. Quantitative analysis of benzo[a]pyrene biotransformation and adduct formation in Ahr knockout mice. Toxicol Lett. 2006;167(3):173–82. https://doi.org/10.1016/j.toxlet.2006.09.005. (Epub 2006 Oct 16 PMID: 17049425).

    Article  CAS  PubMed  Google Scholar 

  56. Wong K-K, Jacks T, Dranoff G. NF-kappaB fans the flames of lung carcinogenesis. Cancer Prev Res (Phila). 2010;3(4):403–5. https://doi.org/10.1158/1940-6207.CAPR-10-0042.

    Article  CAS  PubMed  Google Scholar 

  57. Chen P-H, Chang H, Chang JT, Lin P. Aryl hydrocarbon receptor in association with RelA modulates IL-6 expression in non-smoking lung cancer. Oncogene. 2012;31(20):2555–65. https://doi.org/10.1038/onc.2011.438.

    Article  CAS  PubMed  Google Scholar 

  58. Dalwadi H, et al. Cyclooxygenase-2-dependent activation of signal transducer and activator of transcription 3 by interleukin-6 in non-small cell lung cancer. Clin Cancer Res Off J Am Assoc Cancer Res. 2005;11(21):7674–82. https://doi.org/10.1158/1078-0432.CCR-05-1205.

    Article  CAS  Google Scholar 

  59. Diry M, et al. Activation of the dioxin/aryl hydrocarbon receptor (AhR) modulates cell plasticity through a JNK-dependent mechanism. Oncogene. 2006;25(40):5570–4. https://doi.org/10.1038/sj.onc.1209553.

    Article  CAS  PubMed  Google Scholar 

  60. Rico de Souza A, Zago M, Pollock SJ, Sime PJ, Phipps RP, Baglole CJ. Genetic ablation of the aryl hydrocarbon receptor causes cigarette smoke-induced mitochondrial dysfunction and apoptosis. J Biol Chem. 2011;286(50):43214–28. https://doi.org/10.1074/jbc.M111.258764.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Maltepe E, Schmidt JV, Baunoch D, Bradfield CA, Simon MC. Abnormal angiogenesis and responses to glucose and oxygen deprivation in mice lacking the protein ARNT. Nature. 1997;386(6623):403–7. https://doi.org/10.1038/386403a0.

    Article  CAS  PubMed  Google Scholar 

  62. Roman AC, Carvajal-Gonzalez JM, Rico-Leo EM, Fernandez-Salguero PM. Dioxin receptor deficiency impairs angiogenesis by a mechanism involving VEGF-A depletion in the endothelium and transforming growth factor-beta overexpression in the stroma. J Biol Chem. 2009;284(37):25135–48. https://doi.org/10.1074/jbc.M109.013292.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Wang JH, Trigg CJ, Devalia JL, Jordan S, Davies RJ. Effect of inhaled beclomethasone dipropionate on expression of proinflammatory cytokines and activated eosinophils in the bronchial epithelium of patients with mild asthma. J Allergy Clin Immunol. 1994;94(6 Pt 1):1025–34. https://doi.org/10.1016/0091-6749(94)90121-x.

    Article  CAS  PubMed  Google Scholar 

  64. Wong PS, Vogel CF, Kokosinski K, Matsumura F. Arylhydrocarbon receptor activation in NCI-H441 cells and C57BL/6 mice: possible mechanisms for lung dysfunction. Am J Respir Cell Mol Biol. 2010;42(2):210–7. https://doi.org/10.1165/rcmb.2008-0228OC.

    Article  CAS  PubMed  Google Scholar 

  65. White KE, et al. Prostaglandin E2 mediates IL-1β-related fibroblast mitogenic effects in acute lung injury through differential utilization of prostanoid receptors1. J Immunol. 2008;180(1):637–46. https://doi.org/10.4049/jimmunol.180.1.637.

    Article  CAS  PubMed  Google Scholar 

  66. Kopf PG, Walker MK. 2,3,7,8-tetrachlorodibenzo-p-dioxin increases reactive oxygen species production in human endothelial cells via induction of cytochrome P4501A1. Toxicol Appl Pharmacol. 2010;245(1):91–9. https://doi.org/10.1016/j.taap.2010.02.007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Murray JJ, et al. Release of prostaglandin D2 into human airways during acute antigen challenge. N Engl J Med. 1986;315(13):800–4. https://doi.org/10.1056/NEJM198609253151304.

    Article  CAS  PubMed  Google Scholar 

  68. Chiba T, et al. Possible novel receptor for PGD2 on human bronchial epithelial cells. Int Arch Allergy Immunol. 2007;143(Suppl. 1):23–7. https://doi.org/10.1159/000101400.

    Article  CAS  PubMed  Google Scholar 

  69. Seltzer J, et al. O3-induced change in bronchial reactivity to methacholine and airway inflammation in humans. J Appl Physiol. 1986;60(4):1321–6. https://doi.org/10.1152/jappl.1986.60.4.1321.

    Article  CAS  PubMed  Google Scholar 

  70. Saetta M, Turato G, Maestrelli P, Mapp CE, Fabbri LM. Cellular and structural bases of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2001;163(6):1304–9. https://doi.org/10.1164/AJRCCM.163.6.2009116. PMID: 11371392.

    Article  Google Scholar 

  71. Kirkham P, Rahman I. Oxidative stress in asthma and COPD: antioxidants as a therapeutic strategy. Pharmacol Ther. 2006;111(2):476–94. https://doi.org/10.1016/j.pharmthera.2005.10.015.

    Article  CAS  PubMed  Google Scholar 

  72. Tsuji G, et al. An environmental contaminant, benzo(a)pyrene, induces oxidative stress-mediated interleukin-8 production in human keratinocytes via the aryl hydrocarbon receptor signaling pathway. J Dermatol Sci. 2011;62(1):42–9. https://doi.org/10.1016/j.jdermsci.2010.10.017.

    Article  CAS  PubMed  Google Scholar 

  73. Martinez JM, Afshari CA, Bushel PR, Masuda A, Takahashi T, Walker NJ. Differential toxicogenomic responses to 2,3,7,8-tetrachlorodibenzo-p-dioxin in malignant and nonmalignant human airway epithelial cells. Toxicol Sci. 2002;69(2):409–23. https://doi.org/10.1093/toxsci/69.2.409.

    Article  CAS  PubMed  Google Scholar 

  74. Standiford T, et al. Interleukin-8 gene expression by a pulmonary epithelial cell line: a model for cytokine networks in the lung. J Clin Invest. 1991;86:1945–53. https://doi.org/10.1172/JCI114928.

    Article  Google Scholar 

  75. Busse W, Elias J, Sheppard D, Banks-Schlegel S. Airway remodeling and repair. Am J Respir Crit Care Med. 1999;160(3):1035–42. https://doi.org/10.1164/AJRCCM.160.3.9902064.

    Article  CAS  PubMed  Google Scholar 

  76. Sumi Y, Hamid Q. Airway remodeling in asthma. Allergol Int. 2007;56(4):341–8. https://doi.org/10.2332/allergolint.R-07-153.

    Article  CAS  PubMed  Google Scholar 

  77. Guo J, et al. Expression of genes in the TGF-beta signaling pathway is significantly deregulated in smooth muscle cells from aorta of aryl hydrocarbon receptor knockout mice. Toxicol Appl Pharmacol. 2004;194:79–89. https://doi.org/10.1016/j.taap.2003.09.002.

    Article  CAS  PubMed  Google Scholar 

  78. Martey CA, Baglole CJ, Gasiewicz TA, Sime PJ, Phipps RP. The aryl hydrocarbon receptor is a regulator of cigarette smoke induction of the cyclooxygenase and prostaglandin pathways in human lung fibroblasts. Am J Physiol Lung Cell Mol Physiol. 2005;289(3):L391–9. https://doi.org/10.1152/ajplung.00062.2005.

    Article  CAS  PubMed  Google Scholar 

  79. Profita M, et al. Chronic obstructive pulmonary disease and neutrophil infiltration: role of cigarette smoke and cyclooxygenase products. Am J Physiol Cell Mol Physiol. 2010;298(2):L261–9. https://doi.org/10.1152/ajplung.90593.2008.

    Article  CAS  Google Scholar 

  80. Beamer CA, Shepherd DM. Role of the aryl hydrocarbon receptor (AhR) in lung inflammation. Semin Immunopathol. 2013;35(6):693–704. https://doi.org/10.1007/s00281-013-0391-7.

    Article  CAS  PubMed  Google Scholar 

  81. Kerkvliet NI. AHR-mediated immunomodulation: the role of altered gene transcription. Biochem Pharmacol. 2009;77(4):746–60. https://doi.org/10.1016/j.bcp.2008.11.021.

    Article  CAS  PubMed  Google Scholar 

  82. Chiba T, Chihara J, Furue M. Role of the arylhydrocarbon receptor (AhR) in the pathology of asthma and COPD. J Allergy. 2012;2012:372384. https://doi.org/10.1155/2012/372384.

    Article  CAS  Google Scholar 

  83. Hanlon PR, Ganem LG, Cho YC, Yamamoto M, Jefcoate CR. AhR- and ERK-dependent pathways function synergistically to mediate 2,3,7,8-tetrachlorodibenzo-p-dioxin suppression of peroxisome proliferator-activated receptor-gamma1 expression and subsequent adipocyte differentiation. Toxicol Appl Pharmacol. 2003;189(1):11–27. https://doi.org/10.1016/s0041-008x(03)00083-8.

    Article  CAS  PubMed  Google Scholar 

  84. Cho YC, Zheng W, Yamamoto M, Liu X, Hanlon PR, Jefcoate CR. Differentiation of pluripotent C3H10T1/2 cells rapidly elevates CYP1B1 through a novel process that overcomes a loss of Ah Receptor. Arch Biochem Biophys. 2005;439(2):139–53. https://doi.org/10.1016/j.abb.2005.04.025.

    Article  CAS  PubMed  Google Scholar 

  85. Muranski P, Restifo NP. Essentials of Th17 cell commitment and plasticity. Blood. 2013;121(13):2402–14. https://doi.org/10.1182/blood-2012-09-378653.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Tauchi M, et al. Constitutive expression of aryl hydrocarbon receptor in keratinocytes causes inflammatory skin lesions. Mol Cell Biol. 2005;25(21):9360–8. https://doi.org/10.1128/MCB.25.21.9360-9368.2005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Marcus RS, Holsapple MP, Kaminski NE. Lipopolysaccharide activation of murine splenocytes and splenic B cells increased the expression of aryl hydrocarbon receptor and aryl hydrocarbon receptor nuclear translocator. J Pharmacol Exp Ther. 1998;287(3):1113–8.

    CAS  PubMed  Google Scholar 

  88. Takenaka H, Zhang K, Diaz-Sanchez D, Tsien A, Saxon A. Enhanced human IgE production results from exposure to the aromatic hydrocarbons from diesel exhaust: direct effects on B-cell IgE production. J Allergy Clin Immunol. 1995;95(1 Pt 1):103–15. https://doi.org/10.1016/s0091-6749(95)70158-3.

    Article  CAS  PubMed  Google Scholar 

  89. Ivanova EA, Orekhov AN. T helper lymphocyte subsets and plasticity in autoimmunity and cancer: an overview. Biomed Res Int. 2015;2015:327470. https://doi.org/10.1155/2015/327470.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Gu C, Wu L, Li X. IL-17 family: cytokines, receptors and signaling. Cytokine. 2013;64(2):477–85. https://doi.org/10.1016/j.cyto.2013.07.022.

    Article  CAS  PubMed  Google Scholar 

  91. Ramirez JM, et al. Activation of the aryl hydrocarbon receptor reveals distinct requirements for IL-22 and IL-17 production by human T helper cells. Eur J Immunol. 2010;40(9):2450–9. https://doi.org/10.1002/eji.201040461.

    Article  CAS  PubMed  Google Scholar 

  92. Ishihara Y, Kado SY, Hoeper C, Harel S, Vogel CFA. Role of NF-kB RelB in aryl hydrocarbon receptor-mediated ligand specific effects. Int J Mol Sci. 2019. https://doi.org/10.3390/ijms20112652.

    Article  PubMed  PubMed Central  Google Scholar 

  93. Kimura A, Naka T, Nohara K, Fujii-Kuriyama Y, Kishimoto T. Aryl hydrocarbon receptor regulates Stat1 activation and participates in the development of Th17 cells. Proc Natl Acad Sci USA. 2008;105(28):9721–6. https://doi.org/10.1073/pnas.0804231105.

    Article  PubMed  PubMed Central  Google Scholar 

  94. Vogel CFA, Sciullo E, Li W, Wong P, Lazennec G, Matsumura F. RelB, a new partner of aryl hydrocarbon receptor-mediated transcription. Mol Endocrinol. 2007;21(12):2941–55. https://doi.org/10.1210/me.2007-0211.

    Article  CAS  PubMed  Google Scholar 

  95. Busbee PB, et al. Indole-3-carbinol prevents colitis and associated microbial dysbiosis in an IL-22-dependent manner. JCI Insight. 2020. https://doi.org/10.1172/jci.insight.127551.

    Article  PubMed  PubMed Central  Google Scholar 

  96. Beamer CA, Kreitinger JM, Cole SL, Shepherd DM. Targeted deletion of the aryl hydrocarbon receptor in dendritic cells prevents thymic atrophy in response to dioxin. Arch Toxicol. 2019;93(2):355–68. https://doi.org/10.1007/s00204-018-2366-x.

    Article  CAS  PubMed  Google Scholar 

  97. Camacho IA, Singh N, Hegde VL, Nagarkatti M, Nagarkatti PS. Treatment of mice with 2,3,7,8-tetrachlorodibenzo-p-dioxin leads to aryl hydrocarbon receptor-dependent nuclear translocation of NF-kappaB and expression of Fas ligand in thymic stromal cells and consequent apoptosis in T cells. J Immunol. 2005;175(1):90–103. https://doi.org/10.4049/jimmunol.175.1.90.

    Article  CAS  PubMed  Google Scholar 

  98. Fullerton AM, Roth RA, Ganey PE. 2,3,7,8-TCDD enhances the sensitivity of mice to concanavalin A immune-mediated liver injury. Toxicol Appl Pharmacol. 2013;266(2):317–27. https://doi.org/10.1016/j.taap.2012.11.009.

    Article  CAS  PubMed  Google Scholar 

  99. Neamah WH, et al. AhR activation leads to massive mobilization of myeloid-derived suppressor cells with immunosuppressive activity through regulation of CXCR2 and MicroRNA miR-150-5p and miR-543-3p that target anti-inflammatory genes. J Immunol. 2019;203(7):1830–44. https://doi.org/10.4049/jimmunol.1900291.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Neamah WH, Busbee PB, Alghetaa H, Abdulla OA, Nagarkatti M, Nagarkatti P. AhR activation leads to alterations in the gut microbiome with consequent effect on induction of myeloid derived suppressor cells in a CXCR2-dependent manner. Int J Mol Sci. 2020. https://doi.org/10.3390/ijms21249613.

    Article  PubMed  PubMed Central  Google Scholar 

  101. Singh NP, Singh UP, Singh B, Price RL, Nagarkatti M, Nagarkatti PS. Activation of aryl hydrocarbon receptor (AhR) leads to reciprocal epigenetic regulation of FoxP3 and IL-17 expression and amelioration of experimental colitis. PLoS One. 2011;6(8):e23522. https://doi.org/10.1371/journal.pone.0023522.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Li S, et al. Aryl hydrocarbon receptor signaling cell intrinsically inhibits intestinal group 2 innate lymphoid cell function. Immunity. 2018;49(5):915-928.e5. https://doi.org/10.1016/j.immuni.2018.09.015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Lund AK, Goens MB, Nuñez BA, Walker MK. Characterizing the role of endothelin-1 in the progression of cardiac hypertrophy in aryl hydrocarbon receptor (AhR) null mice. Toxicol Appl Pharmacol. 2006;212(2):127–35. https://doi.org/10.1016/j.taap.2005.07.005.

    Article  CAS  PubMed  Google Scholar 

  104. Ichihara S, et al. Ablation of aryl hydrocarbon receptor promotes angiotensin II-induced cardiac fibrosis through enhanced c-Jun/HIF-1α signaling. Arch Toxicol. 2019;93(6):1543–53. https://doi.org/10.1007/s00204-019-02446-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Andreola F, Fernandez-Salguero PM, Chiantore MV, Petkovich MP, Gonzalez FJ, De Luca LM. Aryl hydrocarbon receptor knockout mice (AHR-/-) exhibit liver retinoid accumulation and reduced retinoic acid metabolism. Cancer Res. 1997;57(14):2835–8.

    CAS  PubMed  Google Scholar 

  106. Andreola F, et al. Mouse liver CYP2C39 is a novel retinoic acid 4-hydroxylase. Its down-regulation offers a molecular basis for liver retinoid accumulation and fibrosis in aryl hydrocarbon receptor-null mice. J Biol Chem. 2004;279(5):3434–8. https://doi.org/10.1074/jbc.M305832200.

    Article  CAS  PubMed  Google Scholar 

  107. Andreola F, et al. Reversal of liver fibrosis in aryl hydrocarbon receptor null mice by dietary vitamin A depletion. Hepatology. 2004;39(1):157–66. https://doi.org/10.1002/hep.20004.

    Article  CAS  PubMed  Google Scholar 

  108. Corchero J, Martín-Partido G, Dallas SL, Fernández-Salguero PM. Liver portal fibrosis in dioxin receptor-null mice that overexpress the latent transforming growth factor-beta-binding protein-1. Int J Exp Pathol. 2004;85(5):295–302. https://doi.org/10.1111/j.0959-9673.2004.00397.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Tian J, Feng Y, Fu H, Xie HQ, Jiang JX, Zhao B. The aryl hydrocarbon receptor: a key bridging molecule of external and internal chemical signals. Environ Sci Technol. 2015;49(16):9518–31. https://doi.org/10.1021/acs.est.5b00385.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Lamb CL, et al. Aryl hydrocarbon receptor activation by TCDD modulates expression of extracellular matrix remodeling genes during experimental liver fibrosis. Biomed Res Int. 2016;2016:5309328. https://doi.org/10.1155/2016/5309328.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Mohammadi-Bardbori A, Bastan F, Akbarizadeh A-R. The highly bioactive molecule and signal substance 6-formylindolo[3,2-b]carbazole (FICZ) plays bi-functional roles in cell growth and apoptosis in vitro. Arch Toxicol. 2017;91(10):3365–72. https://doi.org/10.1007/s00204-017-1950-9.

    Article  CAS  PubMed  Google Scholar 

  112. Farmahin R, Crump D, O’Brien JM, Jones SP, Kennedy SW. Time-dependent transcriptomic and biochemical responses of 6-formylindolo[3,2-b]carbazole (FICZ) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are explained by AHR activation time. Biochem Pharmacol. 2016;115:134–43. https://doi.org/10.1016/j.bcp.2016.06.005.

    Article  CAS  PubMed  Google Scholar 

  113. Smith BW, Stanford EA, Sherr DH, Murphy GJ. Genome editing of the CYP1A1 locus in iPSCs as a platform to map AHR expression throughout human development. Stem Cells Int. 2016;2016:2574152. https://doi.org/10.1155/2016/2574152.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Wincent E, Kubota A, Timme-Laragy A, Jönsson ME, Hahn ME, Stegeman JJ. Biological effects of 6-formylindolo[3,2-b]carbazole (FICZ) in vivo are enhanced by loss of CYP1A function in an Ahr2-dependent manner. Biochem Pharmacol. 2016;110–111:117–29. https://doi.org/10.1016/j.bcp.2016.04.012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Sibilano R, et al. The aryl hydrocarbon receptor modulates acute and late mast cell responses. J Immunol. 2012;189(1):120–7. https://doi.org/10.4049/jimmunol.1200009.

    Article  CAS  PubMed  Google Scholar 

  116. Xie G, Peng Z, Raufman J-P. Src-mediated aryl hydrocarbon and epidermal growth factor receptor cross talk stimulates colon cancer cell proliferation. Am J Physiol Gastrointest Liver Physiol. 2012;302(9):G1006–15. https://doi.org/10.1152/ajpgi.00427.2011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Liu M, et al. Emerging biological functions of IL-17A: a new target in chronic obstructive pulmonary disease? Front Pharmacol. 2021;12:695957. https://doi.org/10.3389/fphar.2021.695957.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Hattori N, et al. Compounds in cigarette smoke induce EGR1 expression via the AHR, resulting in apoptosis and COPD. J Biochem. 2022;172(6):365–76. https://doi.org/10.1093/jb/mvac077.

    Article  CAS  PubMed  Google Scholar 

  119. Pollet M, et al. The AHR represses nucleotide excision repair and apoptosis and contributes to UV-induced skin carcinogenesis. Cell Death Differ. 2018;25(10):1823–36. https://doi.org/10.1038/s41418-018-0160-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Bekki K, et al. The aryl hydrocarbon receptor (AhR) mediates resistance to apoptosis induced in breast cancer cells. Pestic Biochem Physiol. 2015;120:5–13. https://doi.org/10.1016/j.pestbp.2014.12.021.

    Article  CAS  PubMed  Google Scholar 

  121. Zhang X, et al. The aryl hydrocarbon receptor ligand ITE inhibits cell proliferation and migration and enhances sensitivity to drug-resistance in hepatocellular carcinoma. J Cell Physiol. 2021;236(1):178–92. https://doi.org/10.1002/jcp.29832.

    Article  CAS  PubMed  Google Scholar 

  122. Vogel CFA, et al. Pathogenesis of aryl hydrocarbon receptor-mediated development of lymphoma is associated with increased cyclooxygenase-2 expression. Am J Pathol. 2007;171(5):1538–48. https://doi.org/10.2353/ajpath.2007.070406.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Raggi F, et al. Divergent effects of dioxin- or non-dioxin-like polychlorinated biphenyls on the apoptosis of primary cell culture from the mouse pituitary gland. PLoS One. 2016;11(1):e0146729. https://doi.org/10.1371/journal.pone.0146729.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

Our research is supported by the University Grants Commission (Govt. of India), the Department of Biotechnology (Govt. of India), the Science and Engineering Research Board (Govt. of India), and the Department of Science and Technology (Govt. of India).

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  1. Department of Life Sciences, Presidency University, Kolkata, 700073, India

    Avijit Mandal, Nabendu Biswas & Md Nur Alam

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Mandal, A., Biswas, N. & Alam, M.N. Implications of xenobiotic-response element(s) and aryl hydrocarbon receptor in health and diseases. Human Cell 36, 1638–1655 (2023). https://doi.org/10.1007/s13577-023-00931-5

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