ArticleOncogene2012
Aryl hydrocarbon receptor in association with RelA modulates IL-6 expression in non-smoking lung cancer.
Article in Oncogene, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
- Oxidative Potential Versus Biological Effects: A Review on the Relevance of Cell-Free/Abiotic Assays as Predictors of Toxicity from Airborne Particulate Matter.International journal of molecular sciences · 2019Pooled it
- AhR as a Common Denominator in Immunity and Inflammation in Chronic Lung Diseases: Molecular and Clinical Insights.Diseases (Basel, Switzerland) · 2026Review
- Kynurenine Pathway, Nrf2 and NF-κB Cross-Regulation in the CNS: An Overview.Molecular neurobiology · 2026Review
- The landscape of biased agonism in aryl hydrocarbon receptor signaling: current clues and future directions.Frontiers in pharmacology · 2026Review
- Lactucopicrin: A Sesquiterpene Lactone with Anti-Inflammatory Activity Modulates the Crosstalk between NF-kB and AHR Pathways.Journal of medicinal chemistry · 2025Article
- CD103+ dendritic cell-fibroblast crosstalk via TLR9, TDO2, and AHR signaling drives lung fibrogenesis.JCI insight · 2025Article
- Role of Uremic Toxins in Vascular Inflammation Associated with Chronic Kidney Disease.Journal of clinical medicine · 2024Article
- Effect of Elevated Temperatures on Inflammatory Cytokine Release: AnEnvironment & health (Washington, D.C.) · 2024Article
- The chemical composition of secondary organic aerosols regulates transcriptomic and metabolomic signaling in an epithelial-endothelial in vitro coculture.Particle and fibre toxicology · 2024Article
- Targeting aryl hydrocarbon receptor to prevent cancer in barrier organs.Biochemical pharmacology · 2024Review
- Lung cancer associated with combustion particles and fine particulate matter (PMBiochemical pharmacology · 2023Review
- Implications of xenobiotic-response element(s) and aryl hydrocarbon receptor in health and diseases.Human cell · 2023Review
- From Nucleus to Organs: Insights of Aryl Hydrocarbon Receptor Molecular Mechanisms.International journal of molecular sciences · 2022Review
- Particulate matter promotes cancer metastasis through increased HBEGF expression in macrophages.Experimental & molecular medicine · 2022Article
- CYP1A1, VEGFA and Adipokine Responses of Human Adipocytes Co-exposed to PCB126 and Hypoxia.Cells · 2022Article
- Article
- A genome-wide CRISPR screen identifies regulation factors of the TLR3 signalling pathway.Innate immunity · 2020Article
- Aryl Hydrocarbon Receptor Connects Inflammation to Breast Cancer.International journal of molecular sciences · 2020Review
- Response gene to complement-32 promotes cell survival via the NF-κB pathway in non-small-cell lung cancer.Experimental and therapeutic medicine · 2020Article
- Sulforaphane Inhibits the Acquisition of Tobacco Smoke-Induced Lung Cancer Stem Cell-Like PropertiesTheranostics · 2019Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is activated by cigarette smoke. Previously, we demonstrated that AhR is overexpressed in lung adenocarcinomas (ADs). In this study we observed that AhR expression is significantly correlated with nuclear RelA (a nuclear factor-κB (NFκB) subunit) and cytosolic interleukin-6 (IL-6) in 200 non-small cell lung cancer patients, especially among never smokers. Overexpression of AhR increased IL-6 expression in H1355 cells and immortalized human bronchial epithelial cells BEAS-2B. As NFκB inhibitor and knockdown RelA expression greatly reduced constitutive AhR-induced IL-6 expression, we hypothesized that AhR expression, in the absence of exogenous ligand, is able to modulate NFκB activity and subsequently upregulate IL-6 expression, thus promoting the development of lung AD. Specifically, AhR overexpression significantly increased NFκB activity, whereas interference with AhR expression significantly reduced NFκB activity and IL-6 expression in H1355 cells. We demonstrated that AhR associates with RelA in the cytosol and nucleus of human lung cells. Furthermore, AhR overexpression enhanced nuclear localization of AhR and RelA, and increased the association of AhR-RelA with the NFκB response element of the IL-6 promoter. However, p50 was not involved. Our results indicate that AhR, without exposure to a ligand, associates with RelA, which then positively modulates NFκB activity and then upregulates IL-6 expression in human lung cells. Thus we have identified a new mechanism for lung tumorigenesis in non-smokers.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.