Inhibitory or scavenging action of ketoconazole and ciclopiroxolamine against reactive oxygen species released by primed inflammatory cells

Nakashima, Takuji; Sato, Etsuro; Niwano, Yoshimi; Kohno, Masahiro; Muraoka, Wataru; Oda, Tatsuya

doi:10.1111/j.1365-2133.2006.07655.x

Cited by 15 publications

(9 citation statements)

References 42 publications

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“…Similar results that KCZ inhibits ROS released by primed inflammatory cells (Nakashima et al, 2007) and TNFa-induced CCL27, CCL12, and CCL5 production in NHEKs (Kanda and Watanabe, 2006) have been reported; however, the underlying molecular mechanism remains unknown. The present study has identified that AhR and Nrf2, but not AhRR, are critical in the anti-inflammatory effect of KCZ in NHEKs.…”

Section: Discussionsupporting

confidence: 68%

“…The mechanism by which KCZ inhibits skin inflammation has largely depended on its suppression of Malassezia spp, which contributes to the aggravation of seborrheric dermatitis (Gupta et al, 2004) and atopic dermatitis (Darabi et al, 2009). However, KCZ also exerts a direct anti-inflammatory effect (Kanda and Watanabe, 2006;Nakashima et al, 2007), the mechanism of which has remained largely unknown.…”

Section: Introductionmentioning

confidence: 98%

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Identification of Ketoconazole as an AhR-Nrf2 Activator in Cultured Human Keratinocytes: The Basis of Its Anti-Inflammatory Effect

Tsuji

Takahara

Uchi

et al. 2012

Journal of Investigative Dermatology

148

107

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Ketoconazole (KCZ) has been shown to exhibit anti-inflammatory effects in addition to its inhibitory effects against fungi; however, the underlying molecular mechanism remains poorly understood. Aryl hydrocarbon receptor (AhR), a receptor that is activated by polycyclic aromatic hydrocarbons (PAHs) and halogenated aromatic hydrocarbons such as dioxin, is a sensor of the redox system against oxidative stress and regulates nuclear factor-erythroid 2-related factor-2 (Nrf2), a master switch of the redox machinery. To clarify whether KCZ modulates AhR-Nrf2 function leading to redox system activation, cultured human keratinocytes were treated with KCZ. Confocal microscopic analysis revealed that KCZ induced AhR nuclear translocation, resulting in the upregulation of CYP1A1 mRNA and protein expression. Furthermore, KCZ actively switched on Nrf2 nuclear translocation and quinone oxidoreductase 1 expression. Tumor necrosis factor-α- and benzo(a)pyrene (BaP)-induced reactive oxidative species (ROS) and IL-8 production were effectively inhibited by KCZ. Knockdown of either AhR or Nrf2 abolished the inhibitory capacity of KCZ on ROS and IL-8 production. In addition, KCZ-induced Nrf2 activation was canceled by AhR knockdown. Moreover, KCZ inhibited BaP-induced 8-hydroxydeoxyguanosine and IL-8 production. In conclusion, the engagement of AhR by KCZ exhibits the cytoprotective effect mediated by the Nrf2 redox system, which potently downregulates either cytokine-induced (AhR-independent) or PAH-induced (AhR-dependent) oxidative stress.

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Section: Discussionsupporting

confidence: 68%

Section: Introductionmentioning

confidence: 98%

Identification of Ketoconazole as an AhR-Nrf2 Activator in Cultured Human Keratinocytes: The Basis of Its Anti-Inflammatory Effect

Tsuji

Takahara

Uchi

et al. 2012

Journal of Investigative Dermatology

148

107

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“…Reactive oxygen species (ROS) released from inflammatory cells constitutes one of the critical causative factors in inflammatory skin diseases such as atopic dermatitis (14). Several types of inflammatory cells such as neutrophils and macrophages play an important role in acute inflammatory processes.…”

Section: Introductionmentioning

confidence: 99%

“…However, in chronic and overaggressive inflammatory conditions, ROS may also be released into the extracellular compartment, and may cause local propagation of the inflammatory reaction and tissue damage (15,16). Therefore, the inhibition of ROS production or scavenging the released ROS may be important in preventing excess tissue damage in atopic dermatitis (14). …”

Section: Introductionmentioning

confidence: 99%

Anti-inflammatory and Anti-oxidative Effects of Korean Red Ginseng Extract in Human Keratinocytes

Hong

Lyu

2011

Immune Netw

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BackgroundIn this study, we have investigated the effect of Korean red ginseng (KRG) extracts on the production of TNF-α and IL-8 in human keratinocytes. Also, to examine the antioxidative effect of red ginseng extracts, free radical scavenging activity and superoxide dismutase (SOD) activity in human dermal fibroblasts was measured.MethodsTo investigate the effect of KRG in atopic dermatitis, we measured the level of TNF-α and IL-8 secretion in LPS-stimulated human keratinocytes after the treatment of KRG extracts using enzyme-linked immunosorbent assay. Anti-oxidative activity was investigated by measuring 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging and SOD activity.ResultsThe stimulation of human keratinocytes with KRG extracts shifted the LPS-induced cytokine secretion toward a more immunosuppressive response. KRG dose-dependently decreased TNF-α and IL-8 production in HaCaT cells and a significant inhibition of TNF-α was shown when cells were treated with 500 and 1,000 µg/ml of KRG extracts. Additionally, KRG extracts showed DPPH radical scavenging and SOD activity in a dose-dependent manner. Particularly, SOD activities of concentrations higher than 60 µg/ml of KRG extracts were significantly different in human dermal fibroblast cells.ConclusionBased on this study, KRG extracts may be a useful immunosuppressive agent in the treatment of atopic dermatitis.

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“…Antioxidative activity was estimated by the DPPH (1,1-diphenyl-2-picrylhydrazyl)-scavenging method, as described previously. 16) As for hemolytic activity, rabbit erythrocytes were obtained from Nippon Bio-Test Laboratories (Tokyo) and used within 7 d, as described previously. 17) The results of the phylogenetic analysis of the Aspergillus species preserved at NITE based on the ITS-D1/D2 region are shown in Fig.…”

mentioning

confidence: 99%

Comparison of Groupings among Members of the GenusAspergillusBased on Phylogeny and Production of Bioactive Compounds

Anzai¹,

Mayuzumi²,

Nakashima³

et al. 2008

Bioscience, Biotechnology, and Biochemistry

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Inhibitory or scavenging action of ketoconazole and ciclopiroxolamine against reactive oxygen species released by primed inflammatory cells

Cited by 15 publications

References 42 publications

Identification of Ketoconazole as an AhR-Nrf2 Activator in Cultured Human Keratinocytes: The Basis of Its Anti-Inflammatory Effect

Identification of Ketoconazole as an AhR-Nrf2 Activator in Cultured Human Keratinocytes: The Basis of Its Anti-Inflammatory Effect

Anti-inflammatory and Anti-oxidative Effects of Korean Red Ginseng Extract in Human Keratinocytes

Comparison of Groupings among Members of the GenusAspergillusBased on Phylogeny and Production of Bioactive Compounds

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