Protective effects of luteolin against lipopolysaccharide-induced acute lung injury involves inhibition of MEK/ERK and PI3K/Akt pathways in neutrophils
Protective effects of luteolin against lipopolysaccharide-induced acute lung injury involves inhibition of MEK/ERK and PI3K/Akt pathways in neutrophils
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DOI：
10.1038/aps.2010.62
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发表时间：
2010-07-01
影响因子：
8.2
通讯作者：
Kuan, Yu-hsiang
中科院分区：
文献类型：
--
作者：
Lee, Jen-pei;Li, Yi-ching;Kuan, Yu-hsiang
目的：目的：探讨木犀草素对脂多糖（LPS）诱导的小鼠急性肺损伤（ALI）的保护作用及其机制。方法：采用小鼠腹腔内滴注LPS诱导ALI模型。通过测量支气管肺泡灌洗液（BAL）中的细胞计数和蛋白质含量来确定ALI水平。中性粒细胞在体外用甲酰-Met-Leu-Phe（fMLP）或LPS刺激。测定趋化性和超氧阴离子生成以评价中性粒细胞活化。通过Western blot分析了细胞内信号分子在调节中性粒细胞活化中的潜在参与。结果：LPS诱导小鼠ALI，表现为白细胞浸润和蛋白渗漏到肺中。木犀草素减弱LPS诱导的白细胞浸润和蛋白外渗。在细胞研究中，毛地黄黄酮减弱fMLP诱导的中性粒细胞趋化性和呼吸爆发（IC 50分别为0.2 +/- 0.1 μ mol/L和2.2 +/- 0.8 μ mol/L），但在佛波醇肉豆蔻酸酯刺激期间对超氧阴离子产生的影响可忽略不计。此外，毛地黄黄酮有效地阻断MAPK/ERK激酶1/2（MEK），细胞外信号调节激酶（ERK），和Akt磷酸化在fMLP和LPS刺激的neutrophils.Conclusion：这些结果表明，毛地黄黄酮对LPS诱导的小鼠ALI的有益作用，和衰减中性粒细胞趋化性和呼吸爆发毛地黄黄酮涉及的MEK，ERK，和Akt相关的信号通路的阻断。
Aim: To investigate whether luteolin, the major polyphenolic components of Lonicera japonica, has beneficial effects against lipopolysaccharide (LPS)-induced acute lung injury (ALI) and to determine whether the protective mechanism involves anti-inflammatory effects on neutrophils.Methods: ALI was induced with intratracheal instillation of LPS in mice. The level of ALI was determined by measuring the cell count and protein content in bronchoalveolar lavage (BAL) fluid. Neutrophils were stimulated with formyl-Met-Leu-Phe (fMLP) or LPS in vitro. Chemotaxis and superoxide anion generation were measured to evaluate neutrophil activation. The potential involvement of intracellular signaling molecules in regulating neutrophil activation was analyzed by using Western blot.Results: LPS induced ALI in mice, as evidenced with leukocyte infiltration and protein leakage into the lungs. Luteolin attenuated LPS-induced leukocyte infiltration and protein extravasation. In cell studies, luteolin attenuated the fMLP-induced neutrophil chemotaxis and respiratory burst (IC50 0.2 +/- 0.1 mu mol/L and 2.2 +/- 0.8 mu mol/L, respectively), but had a negligible effect on superoxide anion generation during phorbol myristate acetate stimulation. Furthermore luteolin effectively blocked MAPK/ERK kinase 1/2 (MEK), extracellular signal-regulated kinase (ERK), and Akt phosphorylation in fMLP-and LPS-stimulated neutrophils.Conclusion: These results indicate that luteolin has beneficial effects against LPS-induced ALI in mice, and the attenuation of neutrophil chemotaxis and respiratory burst by luteolin involves the blockade of MEK-, ERK-, and Akt-related signaling cascades.