Luteolin suppresses inflammation-associated gene expression by blocking NF-kappaB and AP-1 activation pathway in mouse alveolar macrophages.
Luteolin suppresses inflammation-associated gene expression by blocking NF-kappaB and AP-1 activation pathway in mouse alveolar macrophages.
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叶黄素蛋白通过阻断小鼠肺泡巨噬细胞中的NF-kappab和AP-1激活途径来抑制与炎症相关的基因表达。
DOI：
10.1016/j.lfs.2007.09.028
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发表时间：
2007-11-30
期刊：
影响因子：
6.1
通讯作者：
Hsu SL
中科院分区：
文献类型：
--
作者：
Chen CY;Peng WH;Tsai KD;Hsu SL
木犀草素是一种植物黄酮类化合物，在体内外都具有很强的抗炎作用。然而，木犀草素介导的免疫调节的分子机制尚未完全理解。在这项研究中，我们研究了木犀草素对小鼠肺泡巨噬细胞MH-S和外周巨噬细胞RAW 264.7细胞中一氧化氮（NO）和前列腺素E2（PGE 2）的产生以及诱导型NO合酶（iNOS）、环氧合酶-2（考克斯-2）、肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）表达的影响。木犀草素剂量依赖性地抑制脂多糖（LPS）刺激的巨噬细胞中这些炎症基因和介质的表达和产生。半定量逆转录聚合酶链反应（RT-PCR）进一步证实木犀草素在转录水平抑制LPS诱导的TNF- α、IL-6、iNOS和考克斯-2基因表达。木犀草素还降低LPS激活的巨噬细胞核因子-κ B（NF-κB）的DNA结合活性。此外，毛地黄黄酮还能阻断IκB-α的降解和NF-κB p65亚基的核转位。此外，木犀草素显著抑制LPS诱导的活化蛋白-1（AP-1）的DNA结合活性。我们还发现毛地黄黄酮减弱LPS介导的蛋白激酶B（Akt）和IKK磷酸化，以及活性氧（ROS）的产生。总之，这些数据表明，通过阻断NF-κB和AP-1活化，毛地黄黄酮起到抑制小鼠肺泡巨噬细胞中LPS诱导的炎症事件的作用，并且这种作用至少部分地通过抑制活性氧的产生来介导。我们的观察表明，这种药物可能用于治疗肺部炎症性疾病。
Luteolin, a plant flavonoid, has potent anti-inflammatory properties both in vitro and in vivo. However, the molecular mechanism of luteolin-mediated immune modulation has not been fully understood. In this study, we examined the effects of luteolin on the production of nitric oxide (NO) and prostaglandin E2 (PGE2), as well as the expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) in mouse alveolar macrophage MH-S and peripheral macrophage RAW 264.7 cells. Luteolin dose-dependently inhibited the expression and production of these inflammatory genes and mediators in macrophages stimulated with lipopolysaccharide (LPS). Semi-quantitative reverse-transcription polymerase chain reaction (RT-PCR) assay further confirmed the suppression of LPS-induced TNF- α, IL-6, iNOS and COX-2 gene expression by luteolin at a transcriptional level. Luteolin also reduced the DNA binding activity of nuclear factor-kappa B (NF-κB) in LPS-activated macrophages. Moreover, luteolin blocked the degradation of IκB-α and nuclear translocation of NF-κB p65 subunit. In addition, luteolin significantly inhibited the LPS-induced DNA binding activity of activating protein-1 (AP-1). We also found that luteolin attenuated the LPS-mediated protein kinase B (Akt) and IKK phosphorylation, as well as reactive oxygen species (ROS) production. In sum, these data suggest that, by blocking NF-κB and AP-1 activation, luteolin acts to suppress the LPS-elicited inflammatory events in mouse alveolar macrophages, and this effect was mediated, at least in part, by inhibiting the generation of reactive oxygen species. Our observations suggest a possible therapeutic application of this agent for treating inflammatory disorders in lung.
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影响因子：
5
作者：
Gutierrez-Venegas, Gloria;Kawasaki-Cardenas, Perla;Maldonado-Frias, Silvia
通讯作者：
Maldonado-Frias, Silvia
影响因子：
4.4
作者：
Chandel, NS;Trzyna, WC;Schumacker, PT
通讯作者：
Schumacker, PT
影响因子：
20.3
作者：
Guha, M;O'Connell, MA;Mackman, N
通讯作者：
Mackman, N
影响因子：
3.9
作者：
Cho, MK;Suh, SH;Kim, SG
通讯作者：
Kim, SG
影响因子：
7.3
作者：
Camuesco, D;Comalada, M;Gálvez, J
通讯作者：
Gálvez, J