Yi Chin-Ok, Jeon Byeong Tak, Shin Hyun Joo, Jeong Eun Ae, Chang Ki Churl, Lee Jung Eun, Lee Dong Hoon, Kim Hyun Joon, Kang Sang Soo, Cho Gyeong Jae, Choi Wan Sung, Roh Gu Seob
Department of Anatomy and Neurobiology, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Korea.
Anat Cell Biol. 2011 Sep;44(3):194-203. doi: 10.5115/acb.2011.44.3.194. Epub 2011 Sep 29.
AMP-activated protein kinase (AMPK), an enzyme involved in energy homeostasis, regulates inflammatory responses, but its precise mechanisms are not fully understood. Recent evidence has shown that resveratrol (RES), an AMPK activator, reduces prostaglandin E(2) production in lipopolysaccharide (LPS)-treated microglia. Here, we examined the effect of RES on nuclear factor kappa B (NF-κB) dependent cyclooxygenase (COX)-2 activation in LPS-treated RWA 264.7 macrophages. We found that treatment with RES increased AMPK activation. AMPK and acetyl CoA carboxylase phosphorylation were attenuated in cells treated with LPS+RES, compared to cells treated with LPS alone. RES inhibited tumor necrosis factor (TNF)-α and TNF receptor 1 in LPS-treated cells. Finally, RES inhibited LPS-induced NF-κB translocation into the nucleus and COX-2 expression. Moreover, the effects of 5-aminoimidazole-4-carboxamide ribose and compound C were consistent with the effects of RES in LPS-treated cells. Taken together, these results suggest that the anti-inflammatory action of RES in RAW 264.7 macrophages is dependent on AMPK activation and is associated with inhibition of the LPS-stimulated NF-κB-dependent COX-2 signaling pathway.
AMP 激活的蛋白激酶（AMPK）是一种参与能量稳态调节的酶，它能调控炎症反应，但其确切机制尚未完全明确。近期证据表明，白藜芦醇（RES）作为一种 AMPK 激活剂，可减少脂多糖（LPS）处理的小胶质细胞中前列腺素 E2 的产生。在此，我们研究了 RES 对 LPS 处理的 RAW 264.7 巨噬细胞中核因子κB（NF-κB）依赖性环氧化酶（COX）-2 激活的影响。我们发现，RES 处理可增强 AMPK 的激活。与单独用 LPS 处理的细胞相比，用 LPS + RES 处理的细胞中 AMPK 和乙酰辅酶 A 羧化酶的磷酸化作用减弱。RES 抑制了 LPS 处理细胞中的肿瘤坏死因子（TNF）-α 和 TNF 受体 1。最后，RES 抑制了 LPS 诱导的 NF-κB 向细胞核的转位以及 COX-2 的表达。此外，5-氨基咪唑-4-甲酰胺核糖和化合物 C 的作用与 RES 对 LPS 处理细胞的作用一致。综上所述，这些结果表明 RES 在 RAW 264.7 巨噬细胞中的抗炎作用依赖于 AMPK 的激活，且与抑制 LPS 刺激的 NF-κB 依赖性 COX-2 信号通路相关。
