title: Blockade of the aryl hydrocarbon receptor pathway triggered by dioxin, polycyclic aromatic hydrocarbons and cigarette smoke by Phellinus linteus.
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.
authors.affiliation: Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Yamanashi 409-3898, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Mukai
authors.forename: Ayumi
authors.initials: A
authors.lastname: Kasai
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Hiramatsu
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Hayakawa
authors.forename: Maro
authors.initials: M
authors.lastname: Okamura
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tagawa
authors.forename: Jian
authors.initials: J
authors.lastname: Yao
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Nakamura
authors.forename: Masanori
authors.initials: M
authors.lastname: Kitamura
mesh_terms: D000818:Animals; D001487:Basidiomycota / Q000378:metabolism*; D015152:Blotting, Northern; D045744:Cell Line, Tumor; D032661:Cordyceps / Q000737:chemistry; D004147:Dioxins / Q000494:pharmacology*; D005562:Formazans / Q000494:pharmacology; D007202:Indicators and Reagents; D008114:Liver Neoplasms, Experimental; D051379:Mice; D025282:Mycelium / Q000737:chemistry; D011084:Polycyclic Aromatic Hydrocarbons / Q000494:pharmacology*; D018336:Receptors, Aryl Hydrocarbon / Q000037:antagonists & inhibitors*; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana / Q000737:chemistry*
chemical_list: D004147:Dioxins; D005562:Formazans; D007202:Indicators and Reagents; D011084:Polycyclic Aromatic Hydrocarbons; D018336:Receptors, Aryl Hydrocarbon; D012906:Smoke