The effect of benzo[α]pyrene on expression and signaling cross talk of aryl hydrocarbon receptor and NFATc1 in mouse lung tissue

2014 ◽  
Vol 32 (7) ◽  
pp. 1246-1253 ◽  
Author(s):  
Maliheh Parsa ◽  
Seyed Nasser Ostad ◽  
Seyed Mohammad Hossein Noori Moogahi ◽  
Mohammad Bayat ◽  
Mohammad Hossein Ghahremani
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Lung Tissue ◽  
Cross Talk ◽  
Environmental Pollutants ◽  
Lung Damage ◽  
Mouse Lung ◽  
Aryl Hydrocarbon ◽  
Embedded Blocks ◽  
Mouse Lung Tissue ◽  
Imagej Software

Objective: Polycyclic aromatic hydrocarbons (PAHs) are potent environmental pollutants. Benzo[α]pyrene (B[α]P) is the major compound of PAHs that acts by activating aryl hydrocarbon receptor (AhR) in cells. B[α]P is a known carcinogen and an immunotoxicant; however, its role with regard to nuclear factor of activated T cell (NFAT) pathway is unclear. AhR and NFAT signaling pathways have common roles in pathological functions in immunotoxicity and lung cancer. In this study, the effect of AhR activation on expression and signaling cross talk of AhR and NFATc1 pathways in mouse lung tissue has been investigated. Methods: Swiss albino mice were randomly allocated to five groups and administered with cyclosporin A (CsA) and B[α]P for seven constitutive days. Animals were then killed, and lung tissues were obtained after washing the whole blood. Paraffin-embedded blocks were prepared, and 5 µm sections were cut for histopathological and immunohistochemical assessments. The results were scored by observer and digitally analyzed using ImageJ software. Results: Our data showed that CsA administration resulted in a significant reduction of AhR expression. This effect was partly blocked in mice coadministrated with B[α]P and CsA. NFATc1 expression was also reduced in CsA-treated animals. Furthermore, CsA inhibited the pathological effects of B[α]P in mouse lung tissue. Conclusion: AhR expression is dependent on NFATc1 activation, and NFATc1 inhibition remarkably decreases AhR expression. However, it seems that total expression of NFATc1 is not dependent on AhR expression or activation. Moreover, CsA can prevent B[α]P-induced lung tissue damage, and it remarkably decreases NFATc1 expression. The results from this study point toward the molecular interactions of AhR and NFATc1 activation in lung tissue and the benefit of CsA treatment in B[α]P-induced lung damage.

scholarly journals Expression, Localization, and Activity of the Aryl Hydrocarbon Receptor in the Human Placenta

2018 ◽  
Vol 19 (12) ◽  
pp. 3762 ◽  
Author(s):  
Anaïs Wakx ◽  
Margaux Nedder ◽  
Céline Tomkiewicz-Raulet ◽  
Jessica Dalmasso ◽  
Audrey Chissey ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Human Placenta ◽  
Target Genes ◽  
Environmental Pollutants ◽  
Cell Fractionation ◽  
Protein Levels ◽  
Aryl Hydrocarbon ◽  
Epithelial Barriers ◽  
Expression And Activity

The human placenta is an organ between the blood of the mother and the fetus, which is essential for fetal development. It also plays a role as a selective barrier against environmental pollutants that may bypass epithelial barriers and reach the placenta, with implications for the outcome of pregnancy. The aryl hydrocarbon receptor (AhR) is one of the most important environmental-sensor transcription factors and mediates the metabolism of a wide variety of xenobiotics. Nevertheless, the identification of dietary and endogenous ligands of AhR suggest that it may also fulfil physiological functions with which pollutants may interfere. Placental AhR expression and activity is largely unknown. We established the cartography of AhR expression at transcript and protein levels, its cellular distribution, and its transcriptional activity toward the expression of its main target genes. We studied the profile of AhR expression and activity during different pregnancy periods, during trophoblasts differentiation in vitro, and in a trophoblast cell line. Using diverse methods, such as cell fractionation and immunofluorescence microscopy, we found a constitutive nuclear localization of AhR in every placental model, in the absence of any voluntarily-added exogenous activator. Our data suggest an intrinsic activation of AhR due to the presence of endogenous placental ligands.

scholarly journals Circular RNA profiles in mouse lung tissue induced by radon

2017 ◽  
Vol 22 (1) ◽  
Author(s):  
Weiwei Pei ◽  
Lijing Tao ◽  
Leshuai W. Zhang ◽  
Shuyu Zhang ◽  
Jianping Cao ◽  
...  
Keyword(s):  
Lung Tissue ◽  
Circular Rna ◽  
Mouse Lung ◽  
Mouse Lung Tissue

Normal mouse lung tissue produces a growth-inhibitory factor(s) preferential for mouse monocytic leukemia cells

1989 ◽  
Vol 30 (3) ◽  
pp. 139-144 ◽  
Author(s):  
Togo Ikuta ◽  
Yoshio Honma ◽  
Junko Okabe-Kado ◽  
Takashi Kasukabe ◽  
Motoo Hozumi
Keyword(s):  
Lung Tissue ◽  
Normal Mouse ◽  
Inhibitory Factor ◽  
Leukemia Cells ◽  
Mouse Lung ◽  
Monocytic Leukemia ◽  
Growth Inhibitory Factor ◽  
Growth Inhibitory ◽  
Mouse Lung Tissue

scholarly journals Cross-Talk in the Female Rat Mammary Gland: Influence of Aryl Hydrocarbon Receptor on Estrogen Receptor Signaling

2016 ◽  
Vol 124 (5) ◽  
pp. 601-610 ◽  
Author(s):  
Janina Helle ◽  
Manuela I. Bader ◽  
Annekathrin M. Keiler ◽  
Oliver Zierau ◽  
Günter Vollmer ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Mammary Gland ◽  
Aryl Hydrocarbon Receptor ◽  
Cross Talk ◽  
Female Rat ◽  
Receptor Signaling ◽  
Aryl Hydrocarbon ◽  
Estrogen Receptor Signaling ◽  
Rat Mammary Gland

scholarly journals Identification and Functional Analysis of EPOR+ Tumor-Associated Macrophages in Human Osteosarcoma Lung Metastasis

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Yanxing Li ◽  
Ming Li ◽  
Rong Wei ◽  
Junlong Wu
Keyword(s):  
Lung Metastasis ◽  
Lung Tissue ◽  
Disease Free Survival ◽  
Mouse Lung ◽  
Tumor Associated Macrophages ◽  
Free Survival ◽  
Human Osteosarcoma ◽  
Clinicopathologic Factors ◽  
Mouse Lung Tissue ◽  
Disease Free

Background. Tissue-resident macrophages can be educated to tumor-associated macrophages (TAMs) by the tumor microenvironment and many types of macrophages express erythropoietic receptor (EPOR); However, little is known about the expression of EPOR on TAMs and the identity of EPOR+ TAMs in osteosarcoma lung metastasis has thus far remained elusive. Methods. EPOR-eGFPcre mice were used to determine the expression of EPOR on lung tissue-resident macrophages. Flow cytometry, RT-PCR, and Western blot were examined to define the identity of EPOR+ TAMs in 106 osteosarcoma lung metastasis specimens. Moreover, the clinicopathologic factors and prognosis of patients with CD163+EPOR+ macrophages were compared. Results. We found that a subpopulation of mouse lung tissue-resident macrophages express EPOR and EPO enhances the proliferation of EPOR+ macrophages in mouse lung. A subpopulation of CD163+ macrophages expresses EPOR in human osteosarcoma lung metastasis specimens. CD163+EPOR+TAMs increase 2.5 times in human osteosarcoma lung metastasis tissues; CD206, CD163, and PD1, which are known to have a significant role in TAM function had high expression in CD163+EPOR+ TAMs compared with CD163+EPOR- TAMs. Furthermore, CD163+EPOR+ TAMs had higher M2 marker and cytokine expression in osteosarcoma tissues compared with para-osteosarcoma tissues. EPO enhanced the expression of M2 cytokines in primary CD163+EPOR+ TAMs. Importantly, the percentage of CD163+EPOR+ TAMs had a positive linear association with malignant phenotypes as well as poor disease-free survival and overall survival time. Conclusions. We have characterized TAMs expressing EPOR and CD163+EPOR+ macrophages as TAMs in osteosarcoma lung metastasis patients, which are highly associated with tumor aggressiveness.

Mouse Lung Tissue Slice Culture

2019 ◽  
pp. 297-311 ◽  
Author(s):  
Xinhui Wu ◽  
Eline M. van Dijk ◽  
I. Sophie T. Bos ◽  
Loes E. M. Kistemaker ◽  
Reinoud Gosens
Keyword(s):  
Lung Tissue ◽  
Tissue Slice ◽  
Mouse Lung ◽  
Slice Culture ◽  
Mouse Lung Tissue

scholarly journals A Protective Role of Aryl Hydrocarbon Receptor Repressor in Inflammation and Tumor Growth

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 589 ◽  
Author(s):  
Christoph F. A. Vogel ◽  
Yasuhiro Ishihara ◽  
Claire E. Campbell ◽  
Sarah Y. Kado ◽  
Aimy Nguyen-Chi ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Aryl Hydrocarbon Receptor ◽  
Inflammatory Responses ◽  
Environmental Pollutants ◽  
Protective Role ◽  
Potential Therapeutic Target ◽  
Embryonic Fibroblasts ◽  
Aryl Hydrocarbon ◽  
Enhancer Binding Protein

The aryl hydrocarbon receptor (AhR) is known for mediating the toxicity of environmental pollutants such as dioxins and numerous dioxin-like compounds, and is associated with the promotion of various malignancies, including lymphoma. The aryl hydrocarbon receptor repressor (AhRR), a ligand-independent, transcriptionally inactive AhR-like protein is known to repress AhR signaling through its ability to compete with the AhR for dimerization with the AhR nuclear translocator (ARNT). While AhRR effectively blocks AhR signaling, several aspects of the mechanism of AhRR’s functions are poorly understood, including suppression of inflammatory responses and its putative role as a tumor suppressor. In a transgenic mouse that overexpresses AhRR (AhRR Tg) we discovered that these mice suppress 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)- and inflammation-induced tumor growth after subcutaneous challenge of EL4 lymphoma cells. Using mouse embryonic fibroblasts (MEF) we found that AhRR overexpression suppresses the AhR-mediated anti-apoptotic response. The AhRR-mediated inhibition of apoptotic resistance was associated with a suppressed expression of interleukin (IL)-1β and cyclooxygenase (COX)-2, which was dependent on activation of protein kinase A (PKA) and the CAAT-enhancer-binding protein beta (C/EBPβ). These results provide mechanistic insights into the role of the AhRR to suppress inflammation and highlight the AhRR as a potential therapeutic target to suppress tumor growth.

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