犬尿酸通过 PPARδ/HO-1 依赖性途径减轻脂多糖刺激的内皮细胞中的促炎反应。
Kynurenic acid attenuates pro-inflammatory reactions in lipopolysaccharide-stimulated endothelial cells through the PPARδ/HO-1-dependent pathway.
机构信息
Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea; Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea.
Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea.
出版信息
Mol Cell Endocrinol. 2019 Sep 15;495:110510. doi: 10.1016/j.mce.2019.110510. Epub 2019 Jul 15.
Kynurenic acid (KA) regulates energy homeostasis and alleviates inflammation in adipose tissue but how KA affects the atherosclerotic response in HUVECs remains unclear. We evaluated the effects of KA on lipopolysaccharide (LPS)-induced inflammation and apoptosis in HUVECs. KA enhanced peroxisome proliferator-activated receptor delta (PPARδ) expression in HUVECs and THP-1 cells and suppressed LPS-induced atherosclerotic responses through PPARδ-mediated signaling. Moreover, KA treatment mitigated LPS-induced phosphorylation of nuclear factor kappa B and pro-inflammatory cytokine release in HUVECs and THP-1 cells, and down-regulated adhesion molecules in HUVECs and adhesion of THP-1 cells to HUVECs following LPS treatment. KA treatment decreased LPS-induced inflammation and apoptosis, and also promoted heme oxygenase (HO)-1 expression, which suppresses inflammation in HUVECs. Suppression of PPARδ or HO-1 expression markedly mitigated the effects of KA on atherosclerotic responses in HUVECs. Thus, KA attenuates LPS-induced atherosclerotic responses by suppressing inflammation via the PPARδ/HO-1-dependent pathway.
犬尿酸（KA）可调节能量平衡并减轻脂肪组织中的炎症，但KA 如何影响 HUVECs 的动脉粥样硬化反应尚不清楚。我们评估了 KA 对 HUVECs 中脂多糖（LPS）诱导的炎症和凋亡的影响。KA 增强了 HUVECs 和 THP-1 细胞中的过氧化物酶体增殖物激活受体δ（PPARδ）表达，并通过 PPARδ 介导的信号通路抑制 LPS 诱导的动脉粥样硬化反应。此外，KA 处理减轻了 LPS 诱导的 HUVECs 和 THP-1 细胞中核因子 kappa B 的磷酸化和促炎细胞因子的释放，并下调了 LPS 处理后 HUVECs 中的粘附分子和 THP-1 细胞对 HUVECs 的粘附。KA 处理可减少 LPS 诱导的炎症和凋亡，并促进血红素加氧酶（HO）-1 的表达，从而抑制 HUVECs 中的炎症。抑制 PPARδ 或 HO-1 的表达显著减轻了 KA 对 HUVECs 中动脉粥样硬化反应的影响。因此，KA 通过 PPARδ/HO-1 依赖性途径抑制炎症来减轻 LPS 诱导的动脉粥样硬化反应。
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