2022
Vázquez-Gómez, Gerardo; Karasová, Martina; Tylichová, Zuzana; Kabátková, Markéta; Hampl, Aleš; Matthews, Jason; Neča, Jiří; Ciganek, Miroslav; Machala, Miroslav; Vondráček, Jan
Aryl Hydrocarbon Receptor (AhR) Limits the Inflammatory Responses in Human Lung Adenocarcinoma A549 Cells via Interference with NF-κB Signaling. Journal Article
In: Cells, vol. 11, no. 4, 2022, ISSN: 2073-4409, (Place: Switzerland).
Abstract | Links | BibTeX | Tags: *Environmental Pollutants/toxicity, *Inflammation/pathology, *NF-kappa B/metabolism, *Receptors, A549 Cells, AhR, alveolar epithelial type II cells, Aryl Hydrocarbon/metabolism, cytokines, Humans, Inflammation, NF-κB, prostaglandins
@article{vazquez-gomez_aryl_2022,
title = {Aryl Hydrocarbon Receptor (AhR) Limits the Inflammatory Responses in Human Lung Adenocarcinoma A549 Cells via Interference with NF-κB Signaling.},
author = {Gerardo Vázquez-Gómez and Martina Karasová and Zuzana Tylichová and Markéta Kabátková and Aleš Hampl and Jason Matthews and Jiří Neča and Miroslav Ciganek and Miroslav Machala and Jan Vondráček},
doi = {10.3390/cells11040707},
issn = {2073-4409},
year = {2022},
date = {2022-02-01},
journal = {Cells},
volume = {11},
number = {4},
abstract = {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.},
note = {Place: Switzerland},
keywords = {*Environmental Pollutants/toxicity, *Inflammation/pathology, *NF-kappa B/metabolism, *Receptors, A549 Cells, AhR, alveolar epithelial type II cells, Aryl Hydrocarbon/metabolism, cytokines, Humans, Inflammation, NF-κB, prostaglandins},
pubstate = {published},
tppubtype = {article}
}
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.
2020
Muresan, Ximena Maria; Bouchal, Jan; Culig, Zoran; Souček, Karel
Toll-Like Receptor 3 in Solid Cancer and Therapy Resistance. Journal Article
In: Cancers, vol. 12, no. 11, 2020, ISSN: 2072-6694, (Place: Switzerland).
Abstract | Links | BibTeX | Tags: cytokines, dsRNA, Metastasis, therapy resistance, toll-like receptor 3
@article{muresan_toll-like_2020,
title = {Toll-Like Receptor 3 in Solid Cancer and Therapy Resistance.},
author = {Ximena Maria Muresan and Jan Bouchal and Zoran Culig and Karel Souček},
doi = {10.3390/cancers12113227},
issn = {2072-6694},
year = {2020},
date = {2020-11-01},
journal = {Cancers},
volume = {12},
number = {11},
abstract = {Toll-like receptor 3 (TLR3) is a member of the TLR family, which has been extensively studied for its antiviral function. It is highly expressed in the endosomes of antigen-presenting immune cells and epithelial cells. TLR3 binds specifically double-strand RNAs (dsRNAs), leading to the activation of mainly two downstream pathways: the phosphorylation of IRF3, with subsequent production of type I interferon, and the activation of NF-κB, which drives the production of inflammatory cytokines and chemokines. Several studies have demonstrated TLR3 expression in multiple neoplasia types including breast, prostate, and lung cancer. Most studies were focused on the beneficial role of TLR3 activation in tumor cells, which leads to the production of cytotoxic cytokines and interferons and promotes caspase-dependent apoptosis. Indeed, ligands of this receptor were proposed for the treatment of cancer, also in combination with conventional chemotherapy. In contrast to these findings, recent evidence showed a link between TLR3 and tumor progression, metastasis, and therapy resistance. In the present review, we summarize the current knowledge of the mechanisms through which TLR3 can either lead to tumor regression or promote carcinogenesis as well as the potential of TLR-based therapies in resistant cancer.},
note = {Place: Switzerland},
keywords = {cytokines, dsRNA, Metastasis, therapy resistance, toll-like receptor 3},
pubstate = {published},
tppubtype = {article}
}
Toll-like receptor 3 (TLR3) is a member of the TLR family, which has been extensively studied for its antiviral function. It is highly expressed in the endosomes of antigen-presenting immune cells and epithelial cells. TLR3 binds specifically double-strand RNAs (dsRNAs), leading to the activation of mainly two downstream pathways: the phosphorylation of IRF3, with subsequent production of type I interferon, and the activation of NF-κB, which drives the production of inflammatory cytokines and chemokines. Several studies have demonstrated TLR3 expression in multiple neoplasia types including breast, prostate, and lung cancer. Most studies were focused on the beneficial role of TLR3 activation in tumor cells, which leads to the production of cytotoxic cytokines and interferons and promotes caspase-dependent apoptosis. Indeed, ligands of this receptor were proposed for the treatment of cancer, also in combination with conventional chemotherapy. In contrast to these findings, recent evidence showed a link between TLR3 and tumor progression, metastasis, and therapy resistance. In the present review, we summarize the current knowledge of the mechanisms through which TLR3 can either lead to tumor regression or promote carcinogenesis as well as the potential of TLR-based therapies in resistant cancer.