AMPK Activation Inhibits Expression of Proinflammatory Mediators Through Downregulation of PI3K/p38 MAPK and NF-κB Signaling in Murine Macrophages
AMPK Activation Inhibits Expression of Proinflammatory Mediators Through Downregulation of PI3K/p38 MAPK and NF-κB Signaling in Murine Macrophages
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DOI：
10.1089/dna.2014.2630
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发表时间：
2015-02-01
影响因子：
3.1
通讯作者：
Kao, Shao-Hsuan
中科院分区：
文献类型：
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作者：
Huang, Bee-Piao;Lin, Chun-Hsiang;Kao, Shao-Hsuan
腺苷一磷酸（AMP）激活的蛋白激酶（AMPK）在能量平衡和炎症反应的调节中起着重要作用。本研究旨在研究竹叶核碱基类似物F704对脂多糖（LPS）诱导的小鼠巨噬细胞RAW 264. 7表达促炎介质的抗炎作用。AMIGI-F704可增强AMPK（T172）的磷酸化，但对RAW264.7细胞的存活率无显著影响。进一步的研究表明，FIGIGI-F704降低了LPS诱导的白细胞介素（IL）-6，IL-8，肿瘤坏死因子-α（TNF-α），环氧合酶-2（COX-2）和诱导型一氧化氮合酶（iNOS）的mRNA表达，并抑制了前列腺素E2（PGE（2））和一氧化氮（NO）的产生。此外，AMPK抑制剂化合物C的预处理减弱了AMPGI-F704对LPS诱导的促炎介质的抑制作用。F704还抑制LPS触发的核因子κ B（NF-κ B）、磷脂酰肌醇3-激酶（PI 3 K）和p38丝裂原活化蛋白激酶（p38）的活化，而细胞外信号调节激酶（Erk）1/2和c-Jun N-末端激酶（JNK）的影响不显著。我们的研究结果表明，PDGI-F704可能通过激活AMPK和抑制PI 3 K/P38/NF-κ B B信号通路，从而降低促炎介质的表达，从而对LPS诱导的RAW 264. 7细胞产生抗炎活性，这表明PDGI-F704有助于改善炎症性疾病。
Adenosine monophosphate (AMP)-activated protein kinase (AMPK) plays a central role in energy homeostasis and regulation of inflammatory responses. The present study is aimed to investigate the anti-inflammatory effects of ENERGI-F704, a nucleobase analogue isolated from bamboo leaves, on expression of proinflammatory mediators in murine macrophage RAW264.7 in response to lipopolysaccharide (LPS). ENERGI-F704 enhanced phosphorylation of AMPK(T172) but insignificantly affected the viability of RAW264.7 cells. Further investigation showed that ENERGI-F704 decreased mRNA expression of interleukin (IL)-6, IL-8, tumor necrosis factor-alpha (TNF-alpha), cyclooxygenase-2 (COX2), and inducible nitric oxide synthase (iNOS) induced by LPS, as well as suppressed the production of prostaglandin E2 (PGE(2)) and nitric oxide (NO). Additionally, the inhibitory effects of ENERGI-F704 on the LPS-induced proinflammatory mediators were diminished by pretreatment of AMPK inhibitor Compound C. ENERGI-F704 also inhibited LPS-triggered activation of nuclear factor kappa B (NF-kappa B), phosphatidylinositol 3-kinase (PI3K), and p38 mitogen-activated protein kinase (p38), whereas extracellular signal-regulated kinase (Erk)1/2 and c-Jun N-terminal kinase (JNK) were insignificantly influenced. Our findings indicate that ENERGI-F704 may exert anti-inflammatory activity on RAW264.7 cells in response to LPS through the activation of AMPK and suppression of PI3K/P38/NF-kappa B signaling and the consequent decreased expression of proinflammatory mediators, suggesting that ENERGI-F704 is beneficial to the amelioration of inflammatory disorders.