Blockade of the Aryl Hydrocarbon Receptor Pathway Triggered by Dioxin, Polycyclic Aromatic Hydrocarbons and Cigarette Smoke by Phellinus linteus

Mai Mukai; Ayumi Kasai; Nobuhiko Hiramatsu; Kunihiro Hayakawa; Maro Okamura; Yasuhiro Tagawa; Jian Yao; Tomoyuki Nakamura; Masanori Kitamura

doi:10.1248/bpb.31.1888

Regular Articles

Blockade of the Aryl Hydrocarbon Receptor Pathway Triggered by Dioxin, Polycyclic Aromatic Hydrocarbons and Cigarette Smoke by Phellinus linteus

Mai Mukai, Ayumi Kasai, Nobuhiko Hiramatsu, Kunihiro Hayakawa, Maro Okamura, Yasuhiro Tagawa, Jian Yao, Tomoyuki Nakamura, Masanori Kitamura

Author information

Mai Mukai
Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi
Ayumi Kasai
Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi
Nobuhiko Hiramatsu
Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi
Kunihiro Hayakawa
Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi
Maro Okamura
Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi
Yasuhiro Tagawa
Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi
Jian Yao
Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi
Tomoyuki Nakamura
Applied Fungi Institute, IBI Corporation
Masanori Kitamura
Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi

Keywords: aryl hydrocarbon receptor, cigarette smoke, Phellinus linteus, dioxin, polycyclic aromatic hydrocarbon

JOURNAL FREE ACCESS

2008 Volume 31 Issue 10 Pages 1888-1893

DOI https://doi.org/10.1248/bpb.31.1888

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Abstract

Environmental pollutants including halogenated and polycyclic aromatic hydrocarbons activate the aryl hydrocarbon receptor (AhR) and thereby cause a wide range of pathological changes. Development of AhR antagonists will be useful for prevention and treatment of diseases related to AhR activation. Towards this end, we aimed in the present study at seeking for potential inhibitors of the AhR pathway in mycelial extracts using the dioxin responsive element-based sensing via secreted alkaline phosphatase (DRESSA). Through the screening of 13 mycelia, extracts prepared from Phellinus linteus, Cordyceps militaris and Hericium erinaceum inhibited activation of AhR by 2,3,7,8-tetrachlorodibenzo-p-dioxin, benzo[a]pyrene or 3-methylcholanthrene. Subsequent studies revealed that only Phellinus linteus suppressed activation of AhR and AhR-dependent gene expression triggered by all of these agonists. Cigarette smoke is known to contain a number of halogenated and polycyclic aromatic hydrocarbons. We found that Phellinus linteus has the potential to block activation of AhR and AhR-dependent gene expression triggered by cigarette smoke. Furthermore, the inhibitory effect of Phellinus linteus on the AhR pathway was independent of; 1) depression of AhR or AhR nuclear translocator, and 2) induction of AhR repressor. We conclude that Phellinus linteus contains potent inhibitor(s) of AhR activation and may be useful for prevention of pathologies associated with aberrant activation of AhR.

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