Aryl Hydrocarbon Receptor (AhR) Limits the Inflammatory Responses in Human Lung Adenocarcinoma A549 Cells via Interference with NF-κB Signaling
Jazyk angličtina Země Švýcarsko Médium electronic
Typ dokumentu časopisecké články, práce podpořená grantem
Grantová podpora
18-00145S
Czech Science Foundation
PPLZ no. L200042051
Czech Academy of Sciences
Postdoctoral stay abroad fellowship No. 324651
Consejo Nacional de Ciencia y Tecnología
RVO: 68081707
Czech Academy of Sciences
RO0520
Ministry of Agriculture
PubMed
35203356
PubMed Central
PMC8870046
DOI
10.3390/cells11040707
PII: cells11040707
Knihovny.cz E-zdroje
- Klíčová slova
- AhR, NF-κB, alveolar epithelial type II cells, cytokines, inflammation, prostaglandins,
- MeSH
- buňky A549 MeSH
- látky znečišťující životní prostředí * toxicita MeSH
- lidé MeSH
- NF-kappa B * metabolismus MeSH
- receptory aromatických uhlovodíků * metabolismus MeSH
- zánět * patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- látky znečišťující životní prostředí * MeSH
- NF-kappa B * MeSH
- receptory aromatických uhlovodíků * MeSH
Apart from its role in the metabolism of carcinogens, the aryl hydrocarbon receptor (AhR) has been suggested to be involved in the control of inflammatory responses within the respiratory tract. However, the mechanisms responsible for this are only partially known. In this study, we used A549 cell line, as a human model of lung alveolar type II (ATII)-like cells, to study the functional role of the AhR in control of inflammatory responses. Using IL-1β as an inflammation inducer, we found that the induction of cyclooxygenase-2 and secretion of prostaglandins, as well as expression and release of pro-inflammatory cytokines, were significantly higher in the AhR-deficient A549 cells. This was linked with an increased nuclear factor-κB (NF-κB) activity, and significantly enhanced phosphorylation of its regulators, IKKα/β, and their target IκBα, in the AhR-deficient A549 cells. In line with this, when we mimicked the exposure to a complex mixture of airborne pollutants, using an organic extract of reference diesel exhaust particle mixture, an exacerbated inflammatory response was observed in the AhR-deficient cells, as compared with wild-type A549 cells. Together, the present results indicate that the AhR may act as a negative regulator of the inflammatory response in the A549 model, via a direct modulation of NF-κB signaling. Its role(s) in the control of inflammation within the lung alveoli exposed to airborne pollutants, especially those which simultaneously activate the AhR, thus deserve further attention.
Department of Experimental Biology Faculty of Science Masaryk University 62500 Brno Czech Republic
Department of Nutrition Institute of Basic Medical Sciences University of Oslo 0372 Oslo Norway
Department of Pharmacology and Toxicology Veterinary Research Institute 62100 Brno Czech Republic
International Clinical Research Center St Anne's University Hospital Brno 65691 Brno Czech Republic
Zobrazit více v PubMed
Traboulsi H., Guerrina N., Iu M., Maysinger D., Ariya P., Baglole C.J. Inhaled pollutants: The molecular scene behind respiratory and systemic diseases associated with ultrafine particulate matter. Int. J. Mol. Sci. 2017;18:243. doi: 10.3390/ijms18020243. PubMed DOI PMC
Adler K.B., Fischer B.M., Wright D.T., Cohn L.A., Becker S. Interactions between respiratory epithelial cells and cytokines: Relationships to lung inflammation. Ann. N. Y. Acad. Sci. 1994;725:128–145. doi: 10.1111/j.1749-6632.1994.tb00275.x. PubMed DOI
Nova Z., Skovierova H., Strnadel J., Halasova E., Calkovska A. Short-term versus long-term culture of A549 cells for evaluating the effects of lipopolysaccharide on oxidative stress, surfactant proteins and cathelicidin LL-37. Int. J. Mol. Sci. 2020;21:1148. doi: 10.3390/ijms21031148. PubMed DOI PMC
Fehrenbach H. Alveolar epithelial type II cell: Defender of the alveolus revisited. Respir. Res. 2001;2:33–46. doi: 10.1186/rr36. PubMed DOI PMC
Guillot L., Nathan N., Tabary O., Thouvenin G., Le Rouzic P., Corvol H., Amselem S., Clement A. Alveolar epithelial cells: Master regulators of lung homeostasis. Int. J. Biochem. Cell Biol. 2013;45:2568–2573. doi: 10.1016/j.biocel.2013.08.009. PubMed DOI
Paine R., 3rd, Rolfe M.W., Standiford T.J., Burdick M.D., Rollins B.J., Strieter R.M. MCP-1 expression by rat type II alveolar epithelial cells in primary culture. J. Immunol. 1993;150:4561–4570. PubMed
Standiford T.J., Kunkel S.L., Phan S.H., Rollins B.J., Strieter R.M. Alveolar macrophage-derived cytokines induce monocyte chemoattractant protein-1 expression from human pulmonary type II-like epithelial cells. J. Biol. Chem. 1991;266:9912–9918. doi: 10.1016/S0021-9258(18)92905-4. PubMed DOI
Vanderbilt J.N., Mager E.M., Allen L., Sawa T., Wiener-Kronish J., Gonzalez R., Dobbs L.G. CXC chemokines and their receptors are expressed in type II cells and upregulated following lung injury. Am. J. Respir. Cell Mol. Biol. 2003;29:661–668. doi: 10.1165/rcmb.2002-0227OC. PubMed DOI
Esser C., Rannug A. The aryl hydrocarbon receptor in barrier organ physiology, immunology, and toxicology. Pharmacol. Rev. 2015;67:259–279. doi: 10.1124/pr.114.009001. PubMed DOI
Rothhammer V., Quintana F.J. The aryl hydrocarbon receptor: An environmental sensor integrating immune responses in health and disease. Nat. Rev. Immunol. 2019;19:184–197. doi: 10.1038/s41577-019-0125-8. PubMed DOI
Guarnieri T., Abruzzo P.M., Bolotta A. More than a cell biosensor: Aryl hydrocarbon receptor at the intersection of physiology and inflammation. Am. J. Physiol. Cell Physiol. 2020;318:C1078–C1082. doi: 10.1152/ajpcell.00493.2019. PubMed DOI
Baglole C.J., Maggirwar S.B., Gasiewicz T.A., Thatcher T.H., Phipps R.P., Sime P.J. The aryl hydrocarbon receptor attenuates tobacco smoke-induced cyclooxygenase-2 and prostaglandin production in lung fibroblasts through regulation of the NF-kappaB family member RelB. J. Biol. Chem. 2008;283:28944–28957. doi: 10.1074/jbc.M800685200. PubMed DOI PMC
Rico de Souza A., Zago M., Eidelman D.H., Hamid Q., Baglole C.J. Aryl hydrocarbon receptor (AhR) attenuation of subchronic cigarette smoke-induced pulmonary neutrophilia is associated with retention of nuclear RelB and suppression of intercellular adhesion molecule-1 (ICAM-1) Toxicol. Sci. 2014;140:204–223. doi: 10.1093/toxsci/kfu068. PubMed DOI
Dominguez-Acosta O., Vega L., Estrada-Muniz E., Rodriguez M.S., Gonzalez F.J., Elizondo G. Activation of aryl hydrocarbon receptor regulates the LPS/IFNgamma-induced inflammatory response by inducing ubiquitin-proteosomal and lysosomal degradation of RelA/p65. Biochem. Pharmacol. 2018;155:141–149. doi: 10.1016/j.bcp.2018.06.016. PubMed DOI PMC
Chen P.H., Chang H., Chang J.T., Lin P. Aryl hydrocarbon receptor in association with RelA modulates IL-6 expression in non-smoking lung cancer. Oncogene. 2012;31:2555–2565. doi: 10.1038/onc.2011.438. PubMed DOI
Martey C.A., Baglole C.J., Gasiewicz T.A., Sime P.J., Phipps R.P. 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:L391–L399. doi: 10.1152/ajplung.00062.2005. PubMed DOI
Rogers S., de Souza A.R., Zago M., Iu M., Guerrina N., Gomez A., Matthews J., Baglole C.J. Aryl hydrocarbon receptor (AhR)-dependent regulation of pulmonary miRNA by chronic cigarette smoke exposure. Sci. Rep. 2017;7:40539. doi: 10.1038/srep40539. PubMed DOI PMC
Thatcher T.H., Maggirwar S.B., Baglole C.J., Lakatos H.F., Gasiewicz T.A., Phipps R.P., Sime P.J. Aryl hydrocarbon receptor-deficient mice develop heightened inflammatory responses to cigarette smoke and endotoxin associated with rapid loss of the nuclear factor-kappaB component RelB. Am. J. Pathol. 2007;170:855–864. doi: 10.2353/ajpath.2007.060391. PubMed DOI PMC
Vogel C.F., Sciullo E., Matsumura F. Activation of inflammatory mediators and potential role of ah-receptor ligands in foam cell formation. Cardiovasc. Toxicol. 2004;4:363–373. doi: 10.1385/CT:4:4:363. PubMed DOI
Zago M., Sheridan J.A., Nair P., Rico de Souza A., Gallouzi I.E., Rousseau S., Di Marco S., Hamid Q., Eidelman D.H., Baglole C.J. Aryl hydrocarbon receptor-dependent retention of nuclear HuR suppresses cigarette smoke-induced cyclooxygenase-2 expression independent of DNA-binding. PLoS ONE. 2013;8:e74953. doi: 10.1371/journal.pone.0074953. PubMed DOI PMC
Zago M., Sheridan J.A., Traboulsi H., Hecht E., Zhang Y., Guerrina N., Matthews J., Nair P., Eidelman D.H., Hamid Q., et al. Low levels of the AhR in chronic obstructive pulmonary disease (COPD)-derived lung cells increases COX-2 protein by altering mRNA stability. PLoS ONE. 2017;12:e0180881. doi: 10.1371/journal.pone.0180881. PubMed DOI PMC
Rico de Souza A., Traboulsi H., Wang X., Fritz J.H., Eidelman D.H., Baglole C.J. The aryl hydrocarbon receptor attenuates acute cigarette smoke-induced airway neutrophilia independent of the dioxin response element. Front. Immunol. 2021;12:630427. doi: 10.3389/fimmu.2021.630427. PubMed DOI PMC
Brinchmann B.C., Skuland T., Rambol M.H., Szoke K., Brinchmann J.E., Gutleb A.C., Moschini E., Kubatova A., Kukowski K., Le Ferrec E., et al. Lipophilic components of diesel exhaust particles induce pro-inflammatory responses in human endothelial cells through AhR dependent pathway(s) Part. Fibre Toxicol. 2018;15:21. doi: 10.1186/s12989-018-0257-1. PubMed DOI PMC
O’Driscoll C.A., Owens L.A., Gallo M.E., Hoffmann E.J., Afrazi A., Han M., Fechner J.H., Schauer J.J., Bradfield C.A., Mezrich J.D. Differential effects of diesel exhaust particles on T cell differentiation and autoimmune disease. Part. Fibre Toxicol. 2018;15:35. doi: 10.1186/s12989-018-0271-3. PubMed DOI PMC
Schwarze P.E., Totlandsdal A.I., Lag M., Refsnes M., Holme J.A., Ovrevik J. Inflammation-related effects of diesel engine exhaust particles: Studies on lung cells in vitro. BioMed Res. Int. 2013;2013:685142. doi: 10.1155/2013/685142. PubMed DOI PMC
Diesel Particulate Matter. Certificate of Analysis. National Institute of Standards and Technology; Gaithersburg, MD, USA: 2006.
Andrysík Z., Vondráček J., Marvanová S., Ciganek M., Neča J., Pěnčíková K., Mahadevan B., Topinka J., Baird W.M., Kozubík A., et al. Activation of the aryl hydrocarbon receptor is the major toxic mode of action of an organic extract of a reference urban dust particulate matter mixture: The role of polycyclic aromatic hydrocarbons. Mutat. Res. 2011;714:53–62. doi: 10.1016/j.mrfmmm.2011.06.011. PubMed DOI
Ciganek M., Neča J., Adamec V., Janošek J., Machala M. A combined chemical and bioassay analysis of traffic-emitted polycyclic aromatic hydrocarbons. Sci. Total Environ. 2004;334–335:141–148. doi: 10.1016/j.scitotenv.2004.04.034. PubMed DOI
Rynning I., Neča J., Vrbová K., Líbalová H., Rössner P., Jr., Holme J.A., Gutzkow K.B., Afanou A.K.J., Arnoldussen Y.J., Hruba E., et al. In vitro transformation of human bronchial epithelial cells by diesel exhaust particles: Gene expression profiling and early toxic responses. Toxicol. Sci. 2018;166:51–64. doi: 10.1093/toxsci/kfy183. PubMed DOI PMC
Ricciotti E., FitzGerald G.A. Prostaglandins and inflammation. Arterioscler. Thromb. Vasc. Biol. 2011;31:986–1000. doi: 10.1161/ATVBAHA.110.207449. PubMed DOI PMC
van ‘t Erve T.J., Lih F.B., Kadiiska M.B., Deterding L.J., Eling T.E., Mason R.P. Reinterpreting the best biomarker of oxidative stress: The 8-iso-PGF(2alpha)/PGF(2alpha) ratio distinguishes chemical from enzymatic lipid peroxidation. Free Radic. Biol. Med. 2015;83:245–251. doi: 10.1016/j.freeradbiomed.2015.03.004. PubMed DOI PMC
Moreno J.J. New aspects of the role of hydroxyeicosatetraenoic acids in cell growth and cancer development. Biochem. Pharmacol. 2009;77:1–10. doi: 10.1016/j.bcp.2008.07.033. PubMed DOI
Seo M.J., Oh D.K. Prostaglandin synthases: Molecular characterization and involvement in prostaglandin biosynthesis. Prog. Lipid Res. 2017;66:50–68. doi: 10.1016/j.plipres.2017.04.003. PubMed DOI
Simmons D.L., Botting R.M., Hla T. Cyclooxygenase isozymes: The biology of prostaglandin synthesis and inhibition. Pharmacol. Rev. 2004;56:387–437. doi: 10.1124/pr.56.3.3. PubMed DOI
Aguilera-Montilla N., Chamorro S., Nieto C., Sanchez-Cabo F., Dopazo A., Fernandez-Salguero P.M., Rodriguez-Fernandez J.L., Pello O.M., Andres V., Cuenda A., et al. Aryl hydrocarbon receptor contributes to the MEK/ERK-dependent maintenance of the immature state of human dendritic cells. Blood. 2013;121:e108–e117. doi: 10.1182/blood-2012-07-445106. PubMed DOI
Watanabe I., Tatebe J., Namba S., Koizumi M., Yamazaki J., Morita T. Activation of aryl hydrocarbon receptor mediates indoxyl sulfate-induced monocyte chemoattractant protein-1 expression in human umbilical vein endothelial cells. Circ. J. 2013;77:224–230. doi: 10.1253/circj.CJ-12-0647. PubMed DOI
Hayden M.S., Ghosh S. NF-kappaB, the first quarter-century: Remarkable progress and outstanding questions. Genes Dev. 2012;26:203–234. doi: 10.1101/gad.183434.111. PubMed DOI PMC
Dimitrakopoulos F.D., Kottorou A.E., Kalofonou M., Kalofonos H.P. The fire within: NF-kappaB involvement in non-small cell lung cancer. Cancer Res. 2020;80:4025–4036. doi: 10.1158/0008-5472.CAN-19-3578. PubMed DOI
Ghosh S., May M.J., Kopp E.B. NF-kappa B and Rel proteins: Evolutionarily conserved mediators of immune responses. Annu. Rev. Immunol. 1998;16:225–260. doi: 10.1146/annurev.immunol.16.1.225. PubMed DOI
Karin M., Ben-Neriah Y. Phosphorylation meets ubiquitination: The control of NF-κB activity. Annu. Rev. Immunol. 2000;18:621–663. doi: 10.1146/annurev.immunol.18.1.621. PubMed DOI
Silverman N., Maniatis T. NF-kappaB signaling pathways in mammalian and insect innate immunity. Genes Dev. 2001;15:2321–2342. doi: 10.1101/gad.909001. PubMed DOI
Låg M., Øvrevik J., Refsnes M., Holme J.A. Potential role of polycyclic aromatic hydrocarbons in air pollution-induced non-malignant respiratory diseases. Respir. Res. 2020;21:299. doi: 10.1186/s12931-020-01563-1. PubMed DOI PMC
Nemmar A., Holme J.A., Rosas I., Schwarze P.E., Alfaro-Moreno E. Recent advances in particulate matter and nanoparticle toxicology: A review of the in vivo and in vitro studies. BioMed Res. Int. 2013;2013:279371. doi: 10.1155/2013/279371. PubMed DOI PMC
Øvrevik J., Refsnes M., Låg M., Brinchmann B.C., Schwarze P.E., Holme J.A. Triggering mechanisms and inflammatory effects of combustion exhaust particles with implication for carcinogenesis. Basic Clin. Pharmacol. Toxicol. 2017;121((Suppl. 3)):55–62. doi: 10.1111/bcpt.12746. PubMed DOI
Pěnčíková K., Ciganek M., Neča J., Illés P., Dvořák Z., Vondráček J., Machala M. Modulation of endocrine nuclear receptor activities by polyaromatic compounds present in fractionated extracts of diesel exhaust particles. Sci. Total Environ. 2019;677:626–636. doi: 10.1016/j.scitotenv.2019.04.390. PubMed DOI
Vondráček J., Pěnčíková K., Neča J., Ciganek M., Grycová A., Dvořák Z., Machala M. Assessment of the aryl hydrocarbon receptor-mediated activities of polycyclic aromatic hydrocarbons in a human cell-based reporter gene assay. Pt AEnviron. Pollut. 2017;220:307–316. doi: 10.1016/j.envpol.2016.09.064. PubMed DOI
Li N., Xia T., Nel A.E. The role of oxidative stress in ambient particulate matter-induced lung diseases and its implications in the toxicity of engineered nanoparticles. Free Radic. Biol. Med. 2008;44:1689–1699. doi: 10.1016/j.freeradbiomed.2008.01.028. PubMed DOI PMC
Longhin E., Capasso L., Battaglia C., Proverbio M.C., Cosentino C., Cifola I., Mangano E., Camatini M., Gualtieri M. Integrative transcriptomic and protein analysis of human bronchial BEAS-2B exposed to seasonal urban particulate matter. Environ. Pollut. 2016;209:87–98. doi: 10.1016/j.envpol.2015.11.013. PubMed DOI
Longhin E., Gualtieri M., Capasso L., Bengalli R., Mollerup S., Holme J.A., Ovrevik J., Casadei S., Di Benedetto C., Parenti P., et al. Physico-chemical properties and biological effects of diesel and biomass particles. Environ. Pollut. 2016;215:366–375. doi: 10.1016/j.envpol.2016.05.015. PubMed DOI
Osgood R.S., Upham B.L., Bushel P.R., Velmurugan K., Xiong K.N., Bauer A.K. Secondhand smoke-prevalent polycyclic aromatic hydrocarbon binary mixture-induced specific mitogenic and pro-inflammatory cell signaling events in lung epithelial cells. Toxicol. Sci. 2017;157:156–171. doi: 10.1093/toxsci/kfx027. PubMed DOI PMC
DiNatale B.C., Schroeder J.C., Francey L.J., Kusnadi A., Perdew G.H. Mechanistic insights into the events that lead to synergistic induction of interleukin 6 transcription upon activation of the aryl hydrocarbon receptor and inflammatory signaling. J. Biol. Chem. 2010;285:24388–24397. doi: 10.1074/jbc.M110.118570. PubMed DOI PMC
Hollingshead B.D., Beischlag T.V., Dinatale B.C., Ramadoss P., Perdew G.H. Inflammatory signaling and aryl hydrocarbon receptor mediate synergistic induction of interleukin 6 in MCF-7 cells. Cancer Res. 2008;68:3609–3617. doi: 10.1158/0008-5472.CAN-07-6168. PubMed DOI PMC
Lahoti T.S., Boyer J.A., Kusnadi A., Muku G.E., Murray I.A., Perdew G.H. Aryl hydrocarbon receptor activation synergistically induces lipopolysaccharide-mediated expression of proinflammatory chemokine (c-c motif) ligand 20. Toxicol. Sci. 2015;148:229–240. doi: 10.1093/toxsci/kfv178. PubMed DOI PMC
Liu Y., Mei J., Gonzales L., Yang G., Dai N., Wang P., Zhang P., Favara M., Malcolm K.C., Guttentag S., et al. IL-17A and TNF-alpha exert synergistic effects on expression of CXCL5 by alveolar type II cells in vivo and in vitro. J. Immunol. 2011;186:3197–3205. doi: 10.4049/jimmunol.1002016. PubMed DOI
Thorley A.J., Ford P.A., Giembycz M.A., Goldstraw P., Young A., Tetley T.D. Differential regulation of cytokine release and leukocyte migration by lipopolysaccharide-stimulated primary human lung alveolar type II epithelial cells and macrophages. J. Immunol. 2007;178:463–473. doi: 10.4049/jimmunol.178.1.463. PubMed DOI
Ruan D., So S.P. Prostaglandin E2 produced by inducible COX-2 and mPGES-1 promoting cancer cell proliferation in vitro and in vivo. Life Sci. 2014;116:43–50. doi: 10.1016/j.lfs.2014.07.042. PubMed DOI
Cathcart M.C., O’Byrne K.J., Reynolds J.V., O’Sullivan J., Pidgeon G.P. COX-derived prostanoid pathways in gastrointestinal cancer development and progression: Novel targets for prevention and intervention. Biochim. Biophys. Acta. 2012;1825:49–63. doi: 10.1016/j.bbcan.2011.09.004. PubMed DOI
Liu R., Xu K.P., Tan G.S. Cyclooxygenase-2 inhibitors in lung cancer treatment: Bench to bed. Eur. J. Pharmacol. 2015;769:127–133. doi: 10.1016/j.ejphar.2015.11.007. PubMed DOI
Zhang H., Li Z., Wang K. Combining sorafenib with celecoxib synergistically inhibits tumor growth of non-small cell lung cancer cells in vitro and in vivo. Oncol. Rep. 2014;31:1954–1960. doi: 10.3892/or.2014.3026. PubMed DOI
Nothdurft S., Thumser-Henner C., Breitenbucher F., Okimoto R.A., Dorsch M., Opitz C.A., Sadik A., Esser C., Holzel M., Asthana S., et al. Functional screening identifies aryl hydrocarbon receptor as suppressor of lung cancer metastasis. Oncogenesis. 2020;9:102. doi: 10.1038/s41389-020-00286-8. PubMed DOI PMC
Tsay J.J., Tchou-Wong K.M., Greenberg A.K., Pass H., Rom W.N. Aryl hydrocarbon receptor and lung cancer. Anticancer Res. 2013;33:1247–1256. PubMed PMC
Vancheri C., Mastruzzo C., Sortino M.A., Crimi N. The lung as a privileged site for the beneficial actions of PGE2. Trends Immunol. 2004;25:40–46. doi: 10.1016/j.it.2003.11.001. PubMed DOI
Birrell M.A., Maher S.A., Dekkak B., Jones V., Wong S., Brook P., Belvisi M.G. Anti-inflammatory effects of PGE2 in the lung: Role of the EP4 receptor subtype. Thorax. 2015;70:740–747. doi: 10.1136/thoraxjnl-2014-206592. PubMed DOI PMC
Bärnthaler T., Maric J., Platzer W., Konya V., Theiler A., Hasenöhrl C., Gottschalk B., Trautmann S., Schreiber Y., Graier W.F., et al. The Role of PGE2 in Alveolar Epithelial and Lung Microvascular Endothelial Crosstalk. Sci. Rep. 2017;7:7923. doi: 10.1038/s41598-017-08228-y. PubMed DOI PMC
Øvrevik J., Låg M., Lecureur V., Gilot D., Lagadic-Gossmann D., Refsnes M., Schwarze P.E., Skuland T., Becher R., Holme J.A. AhR and Arnt differentially regulate NF-kappaB signaling and chemokine responses in human bronchial epithelial cells. Cell Commun. Signal. 2014;12:48. doi: 10.1186/s12964-014-0048-8. PubMed DOI PMC
Kurita H., Schnekenburger M., Ovesen J.L., Xia Y., Puga A. The Ah receptor recruits IKKalpha to its target binding motifs to phosphorylate serine-10 in histone H3 required for transcriptional activation. Toxicol. Sci. 2014;139:121–132. doi: 10.1093/toxsci/kfu027. PubMed DOI PMC
Yan B., Liu S., Shi Y., Liu N., Chen L., Wang X., Xiao D., Liu X., Mao C., Jiang Y., et al. Activation of AhR with nuclear IKKalpha regulates cancer stem-like properties in the occurrence of radioresistance. Cell Death Dis. 2018;9:490. doi: 10.1038/s41419-018-0542-9. PubMed DOI PMC
Vineis P., Husgafvel-Pursiainen K. Air pollution and cancer: Biomarker studies in human populations. Carcinogenesis. 2005;26:1846–1855. doi: 10.1093/carcin/bgi216. PubMed DOI
De Kok T.M., Driece H.A., Hogervorst J.G., Briede J.J. Toxicological assessment of ambient and traffic-related particulate matter: A review of recent studies. Mutat. Res. 2006;613:103–122. doi: 10.1016/j.mrrev.2006.07.001. PubMed DOI
Lewtas J. Air pollution combustion emissions: Characterization of causative agents and mechanisms associated with cancer, reproductive, and cardiovascular effects. Mutat. Res. 2007;636:95–133. doi: 10.1016/j.mrrev.2007.08.003. PubMed DOI
Ji J., Upadhyay S., Xiong X., Malmlof M., Sandstrom T., Gerde P., Palmberg L. Multi-cellular human bronchial models exposed to diesel exhaust particles: Assessment of inflammation, oxidative stress and macrophage polarization. Part. Fibre Toxicol. 2018;15:19. doi: 10.1186/s12989-018-0256-2. PubMed DOI PMC
Vogel C.F.A., Van Winkle L.S., Esser C., Haarmann-Stemmann T. The aryl hydrocarbon receptor as a target of environmental stressors—Implications for pollution mediated stress and inflammatory responses. Redox Biol. 2020;34:101530. doi: 10.1016/j.redox.2020.101530. PubMed DOI PMC
Shang Y., Fan L., Feng J., Lv S., Wu M., Li B., Zang Y.S. Genotoxic and inflammatory effects of organic extracts from traffic-related particulate matter in human lung epithelial A549 cells: The role of quinones. Toxicol. In Vitro. 2013;27:922–931. doi: 10.1016/j.tiv.2013.01.008. PubMed DOI
Chang L.W., Chang Y.C., Ho C.C., Tsai M.H., Lin P. Increase of carcinogenic risk via enhancement of cyclooxygenase-2 expression and hydroxyestradiol accumulation in human lung cells as a result of interaction between BaP and 17-beta estradiol. Carcinogenesis. 2007;28:1606–1612. doi: 10.1093/carcin/bgm013. PubMed DOI
Øvrevik J., Refsnes M., Holme J.A., Schwarze P.E., Låg M. Mechanisms of chemokine responses by polycyclic aromatic hydrocarbons in bronchial epithelial cells: Sensitization through toll-like receptor-3 priming. Toxicol. Lett. 2013;219:125–132. doi: 10.1016/j.toxlet.2013.02.014. PubMed DOI
Guerrina N., Traboulsi H., Eidelman D.H., Baglole C.J. The aryl hydrocarbon receptor and the maintenance of lung health. Int. J. Mol. Sci. 2018;19:3882. doi: 10.3390/ijms19123882. PubMed DOI PMC
Beamer C.A., Shepherd D.M. Role of the aryl hydrocarbon receptor (AhR) in lung inflammation. Semin. Immunopathol. 2013;35:693–704. doi: 10.1007/s00281-013-0391-7. PubMed DOI PMC
Murray I.A., Patterson A.D., Perdew G.H. Aryl hydrocarbon receptor ligands in cancer: Friend and foe. Nat. Rev. Cancer. 2014;14:801–814. doi: 10.1038/nrc3846. PubMed DOI PMC