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DPA 衍生物 11S,17S-二羟基 7,9,13,15,19(Z,E,Z,E,Z)-二十二碳五烯酸通过抑制 ROS 产生和 ERK/NF-κB 通路抑制细颗粒物 PM 刺激角质形成细胞 HaCaT 产生白细胞介素 6。

The DPA-derivative 11S, 17S-dihydroxy 7,9,13,15,19 (Z,E,Z,E,Z)-docosapentaenoic acid inhibits IL-6 production by inhibiting ROS production and ERK/NF-κB pathway in keratinocytes HaCaT stimulated with a fine dust PM.

机构信息

Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Republic of Korea.

Department of Biomedical Science and Engineering, Konkuk University, Seoul 05029, Republic of Korea.

出版信息

Ecotoxicol Environ Saf. 2022 Mar 1;232:113252. doi: 10.1016/j.ecoenv.2022.113252. Epub 2022 Jan 29.

Abstract

11 S, 17S-dihydroxy 7,9,13,15,19 (Z,E,Z,E,Z)-docosapentaenoic acid (DoPE) is a derivative of docosapentaenoic acid, a specialized pro-resolving mediator of inflammation such as lipoxins, resolvins, maresins, and protectins. PM is a fine dust particle that induces oxidative stress, DNA damage, inflammation, aging, and cancer. The anti-inflammatory mechanism of DoPE, however, has not yet been elucidated. In these studies, we investigated whether DoPE has anti-inflammatory effects in human keratinocyte HaCaT cells. We demonstrated that DoPE suppressed PM-induced expressions of IL-6 mRNA and protein in human HaCaT keratinocytes. We also investigated the modulating effects of DoPE on reactive oxygen species (ROS) and mitogen-activated protein kinase (MAPK). ROS production, extracellular signal regulated kinase (ERK) phosphorylation, and translocation of nuclear factor-kappa B (NF-kB) p65 and NF-kB activity were suppressed by DoPE in PM-stimulated HaCaT cells. Collectively, our results demonstrated that DoPE inhibited IL-6 expression by reducing ROS generation, suppressing ERK phosphorylation, and inhibiting translocation of NF-kB p65 and NF-kB activity in PM-stimulated HaCaT cells, suggesting that DoPE can be useful for the resolution of the inflammation caused by IL-6.

摘要

11S, 17S-二羟基 7,9,13,15,19(Z,E,Z,E,Z)-二十二碳五烯酸 (DoPE) 是二十二碳五烯酸的衍生物,是一种特殊的炎症内源性分辨率调节剂,如脂氧素、解析素、maresin 和 protectin。PM 是一种细粉尘颗粒,会引起氧化应激、DNA 损伤、炎症、衰老和癌症。然而,DoPE 的抗炎机制尚未阐明。在这些研究中,我们研究了 DoPE 是否对人角质形成细胞 HaCaT 具有抗炎作用。我们证明了 DoPE 抑制了 PM 诱导的人 HaCaT 角质形成细胞中 IL-6 mRNA 和蛋白的表达。我们还研究了 DoPE 对活性氧 (ROS) 和丝裂原活化蛋白激酶 (MAPK) 的调节作用。DoPE 抑制了 PM 刺激的 HaCaT 细胞中 ROS 的产生、细胞外信号调节激酶 (ERK) 磷酸化以及核因子-κB (NF-κB) p65 的核易位和 NF-κB 活性。综上所述,我们的结果表明,DoPE 通过减少 ROS 的产生、抑制 ERK 磷酸化以及抑制 PM 刺激的 HaCaT 细胞中 NF-κB p65 和 NF-κB 活性的核易位,抑制了 IL-6 的表达,表明 DoPE 可用于治疗由 IL-6 引起的炎症。

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