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