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Wogonin inhibits Cytokine-induced TARC/CCL17 Expression by Suppression of NF-κB activation via p38 MAP kinase Signalning Pathways in HaCaT Keratinocytes

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초록

Thymus and activation-regulated chemokine (TARC/CCL-17), produced by keratinocytes, is a CC chemokine known to selectively Th2 type T cells via CCR4+ and is implicated in the development of atopic dermatitis (AD). TARC/CCL17 expression was induced by cytokines such as tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). We recently found that the wogonin, a flavone isolated from Scutellaria baicalensis, suppressed TARC expression via heme oxygenase 1 (HO1) in human keratinocytes induced with mite antigen. However, little is known about the inhibitory mechanism of wogonin on TARC/CCL-17 expression stimulated with cytokines. To investigate the inhibitory mechanism, I determined the inhibitory effects of wogonin on the activation of nuclear factor-κB (NF-κB) and IκBα phosphorylation, and also examined the activation of p38 MAP kainase in HaCaT keratinocytes stimulated with TNF-α and IFN-γ. Wogonin inhibited NF-κB-DNA complex, NF-κB binding activity, and the phosphorylation of IκBα in a dose dependent manner. Wogonin also inhibited the translocation of NF-κB from cytosol to nucleus. Moreover, the phosphorylation of of p38 MAP kinase in the TNF-α and IFN-γ-stimulated HaCaT keratinocytes were suppressed by wogonin in a dose dependent manner. These results suggest that wogonin may inhibit cytokine-induced NF-κB activation by IκBα degradation via suppression of p38 MAP kinase signaling pathway in keratinocytes and modulation of wogonin signaling pathway may be beneficial for the treatment of AD.

Abstract

Thymus and activation-regulated chemokine (TARC/CCL-17), produced by keratinocytes, is a CC chemokine known to selectively Th2 type T cells via CCR4+ and is implicated in the development of atopic dermatitis (AD). TARC/CCL17 expression was induced by cytokines such as tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). We recently found that the wogonin, a flavone isolated from Scutellaria baicalensis, suppressed TARC expression via heme oxygenase 1 (HO1) in human keratinocytes induced with mite antigen. However, little is known about the inhibitory mechanism of wogonin on TARC/CCL-17 expression stimulated with cytokines. To investigate the inhibitory mechanism, I determined the inhibitory effects of wogonin on the activation of nuclear factor-κB (NF-κB) and IκBα phosphorylation, and also examined the activation of p38 MAP kainase in HaCaT keratinocytes stimulated with TNF-α and IFN-γ. Wogonin inhibited NF-κB-DNA complex, NF-κB binding activity, and the phosphorylation of IκBα in a dose dependent manner. Wogonin also inhibited the translocation of NF-κB from cytosol to nucleus. Moreover, the phosphorylation of of p38 MAP kinase in the TNF-α and IFN-γ-stimulated HaCaT keratinocytes were suppressed by wogonin in a dose dependent manner. These results suggest that wogonin may inhibit cytokine-induced NF-κB activation by IκBα degradation via suppression of p38 MAP kinase signaling pathway in keratinocytes and modulation of wogonin signaling pathway may be beneficial for the treatment of AD.

참고문헌 (45)

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Mechanism of Macrophage-Derived Chemokine/CCL22 Production by HaCaT KeratinocytesChizuko Yano, Hidehisa Saeki, Hidemi Nakagawa, Mamitaro Ohtsuki, Mayumi Komine, Shinji Kagami, Yuichiro Tsunemi대한피부과학회 · Annals of Dermatology2015 · 제27권 제2호피부각질세포에서 梔子柏皮湯의 아토피 피부염 개선효과강대길, 김혜윰, 나세원, 손찬옥, 안유미, 윤정주, 은소영, 이윤정, 이호섭, 한병혁, 홍미현한의병리학회 · 동의생리병리학회지2018 · 제32권 제4호2,3-Dimethoxy-2′-hydroxychalcone ameliorates TNF-α-induced ICAM-1 expression and subsequent monocyte adhesiveness via NF-kappaB inhibition and HO-1 induction in HaCaT cells권혁일, 김혜진, 박진서, 안수연, 윤기수, 최수영생화학분자생물학회 · BMB Reports2016 · 제49권 제1호山白菊 열수추출물이 HaCaT 피부각질세포에서 미치는 항염증 효과김근립, 김세중, 이규영, 홍철희대한한방안이비인후피부과학회 · 한방안이비인후피부과학회지2022 · 제35권 제2호Butein, a tetrahydroxychalcone, suppresses pro-inflammatory responses in HaCaT keratinocytes박진서, 서원영, 윤기수, 최수영생화학분자생물학회 · BMB Reports2015 · 제48권 제9호Isoegomaketone Ameliorates Atopic Dermatitis via MAPK and STAT Pathway-based Pro-Inflammatory Cytokine Regulation김예람, 신재영, 조병옥, 진창현, 한아름(사)한국방사선산업학회 · 방사선산업학회지2023 · 제17권 제4호

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