Regulation of anti-inflammatory and anti-oxidative effects by liranaftate through aryl hydrocarbon receptor on human keratinocytes

Masakazu Takahara, Kenjiro Takei, Akiko Hachiya, Yukihiro Mizote, Mika Murai, Yoshiko Sasaki, Fumitaka Ono, Noriko Okabe, Nobutoshi Take, Akiko Masuda, Masutaka Furue

Research output: Contribution to journalArticle

Abstract

The antimycotic drug liranaftate has been shown to have anti-inflammatory effects, but its mechanism of action is largely unknown. Many polycyclic aromatic hydrocarbons and other external chemicals bind to the cytosolic aryl hydrocarbon receptor (AhR), which is abundantly expressed in cultured human keratinocytes. Liranaftate induced nuclear translocation of AhR and nuclear factor-erythroid 2-related factor-2 (Nrf2) from the cytoplasm in the keratinocytes and upregulated mRNA for NAD(P)H : quinone oxidoreductase 1 (Nqo1) and Nrf2. TNFα-induced reactive oxidative species (ROS) and IL-8 production were effectively inhibited by liranaftate. Knockdown of AhR abolished liranaftate-induced Nqo1 and Nrf2 expressions as well as the inhibitory action on IL-8 production, suggesting an AhR-dependent mechanism of action. Additionally, liranaftate upregulated the mRNA expressions of skin barrier proteins such as filaggrin, loricrin and involucrin in an AhR-dependent fashion. These anti-inflammatory effects may partly explain the rapid and potent clinical efficacy against tinea by liranaftate.

Original languageEnglish
Pages (from-to)121-126
Number of pages6
JournalNishinihon Journal of Dermatology
Volume76
Issue number2
DOIs
Publication statusPublished - Jan 1 2014

Fingerprint

Aryl Hydrocarbon Receptors
Keratinocytes
Anti-Inflammatory Agents
Interleukin-8
Messenger RNA
Tinea
Polycyclic Aromatic Hydrocarbons
NAD
liranaftate
human AHR protein
Oxidoreductases
Cytoplasm
Skin
Pharmaceutical Preparations
Proteins

All Science Journal Classification (ASJC) codes

  • Dermatology

Cite this

Regulation of anti-inflammatory and anti-oxidative effects by liranaftate through aryl hydrocarbon receptor on human keratinocytes. / Takahara, Masakazu; Takei, Kenjiro; Hachiya, Akiko; Mizote, Yukihiro; Murai, Mika; Sasaki, Yoshiko; Ono, Fumitaka; Okabe, Noriko; Take, Nobutoshi; Masuda, Akiko; Furue, Masutaka.

In: Nishinihon Journal of Dermatology, Vol. 76, No. 2, 01.01.2014, p. 121-126.

Research output: Contribution to journalArticle

Takahara, Masakazu ; Takei, Kenjiro ; Hachiya, Akiko ; Mizote, Yukihiro ; Murai, Mika ; Sasaki, Yoshiko ; Ono, Fumitaka ; Okabe, Noriko ; Take, Nobutoshi ; Masuda, Akiko ; Furue, Masutaka. / Regulation of anti-inflammatory and anti-oxidative effects by liranaftate through aryl hydrocarbon receptor on human keratinocytes. In: Nishinihon Journal of Dermatology. 2014 ; Vol. 76, No. 2. pp. 121-126.
@article{171d68103b5149b19f551452cfe8a54b,
title = "Regulation of anti-inflammatory and anti-oxidative effects by liranaftate through aryl hydrocarbon receptor on human keratinocytes",
abstract = "The antimycotic drug liranaftate has been shown to have anti-inflammatory effects, but its mechanism of action is largely unknown. Many polycyclic aromatic hydrocarbons and other external chemicals bind to the cytosolic aryl hydrocarbon receptor (AhR), which is abundantly expressed in cultured human keratinocytes. Liranaftate induced nuclear translocation of AhR and nuclear factor-erythroid 2-related factor-2 (Nrf2) from the cytoplasm in the keratinocytes and upregulated mRNA for NAD(P)H : quinone oxidoreductase 1 (Nqo1) and Nrf2. TNFα-induced reactive oxidative species (ROS) and IL-8 production were effectively inhibited by liranaftate. Knockdown of AhR abolished liranaftate-induced Nqo1 and Nrf2 expressions as well as the inhibitory action on IL-8 production, suggesting an AhR-dependent mechanism of action. Additionally, liranaftate upregulated the mRNA expressions of skin barrier proteins such as filaggrin, loricrin and involucrin in an AhR-dependent fashion. These anti-inflammatory effects may partly explain the rapid and potent clinical efficacy against tinea by liranaftate.",
author = "Masakazu Takahara and Kenjiro Takei and Akiko Hachiya and Yukihiro Mizote and Mika Murai and Yoshiko Sasaki and Fumitaka Ono and Noriko Okabe and Nobutoshi Take and Akiko Masuda and Masutaka Furue",
year = "2014",
month = "1",
day = "1",
doi = "10.2336/nishinihonhifu.76.121",
language = "English",
volume = "76",
pages = "121--126",
journal = "Nishinihon Journal of Dermatology",
issn = "0386-9784",
publisher = "Kyushu University, Faculty of Science",
number = "2",

}

TY - JOUR

T1 - Regulation of anti-inflammatory and anti-oxidative effects by liranaftate through aryl hydrocarbon receptor on human keratinocytes

AU - Takahara, Masakazu

AU - Takei, Kenjiro

AU - Hachiya, Akiko

AU - Mizote, Yukihiro

AU - Murai, Mika

AU - Sasaki, Yoshiko

AU - Ono, Fumitaka

AU - Okabe, Noriko

AU - Take, Nobutoshi

AU - Masuda, Akiko

AU - Furue, Masutaka

PY - 2014/1/1

Y1 - 2014/1/1

N2 - The antimycotic drug liranaftate has been shown to have anti-inflammatory effects, but its mechanism of action is largely unknown. Many polycyclic aromatic hydrocarbons and other external chemicals bind to the cytosolic aryl hydrocarbon receptor (AhR), which is abundantly expressed in cultured human keratinocytes. Liranaftate induced nuclear translocation of AhR and nuclear factor-erythroid 2-related factor-2 (Nrf2) from the cytoplasm in the keratinocytes and upregulated mRNA for NAD(P)H : quinone oxidoreductase 1 (Nqo1) and Nrf2. TNFα-induced reactive oxidative species (ROS) and IL-8 production were effectively inhibited by liranaftate. Knockdown of AhR abolished liranaftate-induced Nqo1 and Nrf2 expressions as well as the inhibitory action on IL-8 production, suggesting an AhR-dependent mechanism of action. Additionally, liranaftate upregulated the mRNA expressions of skin barrier proteins such as filaggrin, loricrin and involucrin in an AhR-dependent fashion. These anti-inflammatory effects may partly explain the rapid and potent clinical efficacy against tinea by liranaftate.

AB - The antimycotic drug liranaftate has been shown to have anti-inflammatory effects, but its mechanism of action is largely unknown. Many polycyclic aromatic hydrocarbons and other external chemicals bind to the cytosolic aryl hydrocarbon receptor (AhR), which is abundantly expressed in cultured human keratinocytes. Liranaftate induced nuclear translocation of AhR and nuclear factor-erythroid 2-related factor-2 (Nrf2) from the cytoplasm in the keratinocytes and upregulated mRNA for NAD(P)H : quinone oxidoreductase 1 (Nqo1) and Nrf2. TNFα-induced reactive oxidative species (ROS) and IL-8 production were effectively inhibited by liranaftate. Knockdown of AhR abolished liranaftate-induced Nqo1 and Nrf2 expressions as well as the inhibitory action on IL-8 production, suggesting an AhR-dependent mechanism of action. Additionally, liranaftate upregulated the mRNA expressions of skin barrier proteins such as filaggrin, loricrin and involucrin in an AhR-dependent fashion. These anti-inflammatory effects may partly explain the rapid and potent clinical efficacy against tinea by liranaftate.

UR - http://www.scopus.com/inward/record.url?scp=84905965710&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84905965710&partnerID=8YFLogxK

U2 - 10.2336/nishinihonhifu.76.121

DO - 10.2336/nishinihonhifu.76.121

M3 - Article

AN - SCOPUS:84905965710

VL - 76

SP - 121

EP - 126

JO - Nishinihon Journal of Dermatology

JF - Nishinihon Journal of Dermatology

SN - 0386-9784

IS - 2

ER -