野生苦瓜果实提取物对 C57BL/6J 小鼠和 microRNA-221/222 基因敲除小鼠肺上皮细胞中 ICAM-1 表达的影响：涉及 miR-221/-222/PI3K/AKT/NF-κB 通路。
The effects of wild bitter gourd fruit extracts on ICAM-1 expression in pulmonary epithelial cells of C57BL/6J mice and microRNA-221/222 knockout mice: Involvement of the miR-221/-222/PI3K/AKT/NF-κB pathway.
机构信息
Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Anatomy, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.
出版信息
Phytomedicine. 2018 Mar 15;42:90-99. doi: 10.1016/j.phymed.2018.03.023. Epub 2018 Mar 12.
BACKGROUND
The extracts from wild bitter gourd fruit (WBGE) were reported to possess numerous pharmacological activities. However, the anti-inflammatory effects of WBGE on human lung epithelial cells and the underlying mechanisms have not been determined.
PURPOSE
To evaluate the molecular basis of the effects of WBGE on intercellular adhesion molecule-1 (ICAM-1) expression in alveolar epithelial (A549) cells, C57BL/6 wild-type (WT) mice and microRNA (miR)-221/-222 knockout (KO) mice with or without tumor necrosis factor (TNF-α; 3 ng/ml) treatment.
STUDY DESIGN/METHODS: WT mice and miR-221/-222 KO mice were fed a control diet and divided into four groups (C: control mice; T: treated with TNF-α alone; WBGE/T: pretreated with WBGE and then stimulated with TNF-α; WBGE: treated with WBGE alone). The effects of WBGE on ICAM-1 expression and the related signals in A549 cells and mice with or without TNF-α treatment were examined by Western blot and immunofluorescent staining.
RESULTS
WBGE significantly decreased the TNF-α-induced ICAM-1 expression in A549 cells through the inhibition of phosphoinositide 3-kinase (PI3K)/ protein kinase B (AKT)/ nuclear factor- kappa B (NF-κB)/ inhibitor of NF-κB (IκB) phosphorylation and decreased leukocyte adhesion. In addition, WBGE reduced endogenous ICAM-1 expression and upregulated miR-221/-222 expression. The overexpression of miR-222 decreased PI3K/AKT/NF-κB/IκB and ICAM-1 expression, which resulted in reducing monocyte adhesion. Moreover, WBGE reduced ICAM-1 expression in lung tissues of WT mice with or without TNF-α treatment and upregulated miR-221/222. WBGE did not affect the miR-221/-222 level and had little effect on ICAM-1 expression in miR-221/-222 KO mice.
CONCLUSIONS
These results suggest that WBGE reduced ICAM-1 expression both under in vitro and in vivo conditions. The protective effects were mediated partly through the miR-221/-222/PI3K/AKT/NF-κB pathway.
背景
野生苦瓜果实提取物（WBGE）具有多种药理活性。然而，WBGE 对人肺上皮细胞的抗炎作用及其机制尚未确定。
目的
评估 WBGE 对肺泡上皮（A549）细胞、C57BL/6 野生型（WT）小鼠和微小 RNA（miR）-221/-222 敲除（KO）小鼠中细胞间黏附分子-1（ICAM-1）表达的影响及其分子基础，这些小鼠经肿瘤坏死因子（TNF-α；3ng/ml）处理后。
研究设计/方法：WT 小鼠和 miR-221/-222 KO 小鼠喂食对照饮食，并分为四组（C：对照小鼠；T：仅用 TNF-α处理；WBGE/T：用 WBGE 预处理后用 TNF-α刺激；WBGE：仅用 WBGE 处理）。通过 Western blot 和免疫荧光染色，检测 WBGE 对 TNF-α处理或未处理的 A549 细胞和小鼠中 ICAM-1 表达及相关信号的影响。
结果
WBGE 通过抑制磷酸肌醇 3-激酶（PI3K）/蛋白激酶 B（AKT）/核因子-κB（NF-κB）/NF-κB 抑制剂（IκB）磷酸化，显著降低 TNF-α诱导的 A549 细胞中 ICAM-1 的表达，从而减少白细胞黏附。此外，WBGE 降低内源性 ICAM-1 表达并上调 miR-221/-222 表达。miR-222 的过表达降低了 PI3K/AKT/NF-κB/IκB 和 ICAM-1 的表达，从而减少了单核细胞的黏附。此外，WBGE 降低了 WT 小鼠肺组织中 TNF-α处理或未处理时的 ICAM-1 表达，并上调了 miR-221/222。WBGE 不影响 miR-221/-222 KO 小鼠的 miR-221/-222 水平，对其 ICAM-1 表达影响较小。
结论
这些结果表明，WBGE 降低了体外和体内条件下的 ICAM-1 表达。保护作用部分通过 miR-221/-222/PI3K/AKT/NF-κB 途径介导。
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