Aryl Hydrocarbon Receptor Signaling Is Functional in Immune Cells of Rainbow Trout (Oncorhynchus mykiss).

Jun-Young Song,Anja-Maria Möller,Ayako Casanova-Nakayama,Kei Nakayama,Helmut Segner,Shin-Ichi Kitamura

doi:10.3390/ijms21176323

Jun-Young Song, Anja-Maria Möller + Show 4 more

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https://doi.org/10.3390/ijms21176323

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Abstract

The arylhydrocarbon receptor (AhR) is an important signaling pathway in the immune system of mammals. In addition to its physiological functions, the receptor mediates the immunotoxic actions of a diverse range of environmental contaminants that bind to and activate the AhR, including planar halogenated aromatic hydrocarbons (PHAHs or dioxin-like compounds) and polynuclear aromatic hydrocarbons (PAHs). AhR-binding xenobiotics are immunotoxic not only to mammals but to teleost fish as well. To date, however, it is unknown if the AhR pathway is active in the immune system of fish and thus may act as molecular initiating event in the immunotoxicity of AhR-binding xenobiotics to fish. The present study aims to examine the presence of functional AhR signaling in immune cells of rainbow trout (Oncorhynchus mykiss). Focus is given to the toxicologically relevant AhR2 clade. By means of RT-qPCR and in situ hybdridization, we show that immune cells of rainbow trout express ahr 2α and ahr 2β mRNA; this applies for immune cells isolated from the head kidney and from the peripheral blood. Furthermore, we show that in vivo as well as in vitro exposure to the AhR ligand, benzo(a)pyrene (BaP), causes upregulation of the AhR-regulated gene, cytochrome p4501a, in rainbow trout immune cells, and that this induction is inhibited by co-treatment with an AhR antagonist. Taken together, these findings provide evidence that functional AhR signaling exists in the immune cells of the teleost species, rainbow trout.

Highlights

The arylhydrocarbon receptor (AhR) is a cytosolic protein which belongs to the basic helix-loop-helix-PAS family (Per-ARNT (AhR nuclear translocator)-Sim) [1,2,3]
In order to obtain insight if the AhR is functional in the immune cells, we evaluate whether exposure of trout to BaP induces an upregulation of the AhR-regulated gene, cytochrome P4501A, and whether this can be inhibited by the AhR antagonist, α-naphthoflavone
Unpublished preliminary data from cell sorting experiments of our laboratory are supportive to this interpretation, as we found cell fractions enriched with B cells or ganulocytes to be positive for ahr2 mRNA

Summary

Introduction

The arylhydrocarbon receptor (AhR) is a cytosolic protein which belongs to the basic helix-loop-helix (bHLH)-PAS family (Per (period)-ARNT (AhR nuclear translocator)-Sim (single-minded)) [1,2,3]. Activation of the AhR pathway by environmental contaminants induces a battery of genes involved in the biotransformation of xenobiotics, and it can lead to diverse toxic responses including developmental abnormalities, cancer promotion, liver and renal failure, and immunotoxicity [9,10,11,12] It was this role in mediating the toxicity of dioxins and related compounds why the AhR has attracted much attention in toxicological research, and it was the observation that dioxins can induce biotransformation enzymes like cytochrome P450 monooxygenases which led to the discovery of the AhR [3,13,14]

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