5-Aminoimidazole-4-carboxamide riboside suppresses lipopolysaccharide-induced TNF-α production through inhibition of phosphatidylinositol 3-kinase/Akt activation in RAW 264.7 murine macrophages
5-Aminoimidazole-4-carboxamide riboside suppresses lipopolysaccharide-induced TNF-α production through inhibition of phosphatidylinositol 3-kinase/Akt activation in RAW 264.7 murine macrophages
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DOI：
10.1016/j.bbrc.2004.04.035
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发表时间：
2004-05-28
影响因子：
3.1
通讯作者：
Kang, I
中科院分区：
文献类型：
--
作者：
Jhun, BS;Jin, QR;Kang, I
5-氨基咪唑-4-甲酰胺核苷(AICAR)是一种腺苷类似物，也是一种广泛使用的AMPK激活剂。我们研究了AICAR对内毒素诱导的RAW 264.7巨噬细胞和腹膜巨噬细胞产生肿瘤坏死因子-α的影响及其在RAW 264.7巨噬细胞中的分子机制。AICAR可抑制脂多糖诱导的这些细胞中肿瘤坏死因子-α的mRNA和蛋白水平的升高。AICAR或内毒素均不影响AMPK活性和AMPK的磷酸化。(第172页)和ACC(第79页)。此外，腺苷激酶抑制剂5‘-碘结节杀菌素增强了AICAR对肿瘤坏死因子-α水平的抑制作用。这些结果表明，AICAR对RAW 264.7细胞肿瘤坏死因子-α的抑制作用不依赖于AMPK的激活。此外，腺苷受体拮抗剂8-SPT对AICAR诱导的肿瘤坏死因子-α水平的抑制没有影响。上述结果提示，AICAR对RAW 264.7巨噬细胞的抗炎作用不依赖于AMPK的激活，而可能与抑制脂多糖诱导的PI3-K/Akt通路的激活有关。(C)2004 Elsevier Inc.保留所有权利。
5-Aminoimidazole-4-carboxamide riboside (AICAR) is an adenosine analog and a widely used activator of AMP-activated protein kinase (AMPK). We examined the effect of AICAR on LPS-induced TNF-alpha production in RAW 264.7 and peritoneal macrophages and its molecular mechanism in RAW 264.7 macrophages. Treatment with AICAR inhibited LPS-induced increases in TNF-alpha mRNA and protein levels in these cells. AICAR or LPS did not alter the AMPK activity as well as the phosphorylations of AMPK of. (Thr172) and ACC (Ser79). Moreover, an adenosine kinase inhibitor 5'-iodotubercidin enhanced the Suppressive effect Of AICAR on TNF-alpha levels. These results suggest that the effect of AICAR on TNF-alpha suppression in RAW 264.7 cells is independent of AMPK activation. In addition, an adenosine receptor antagonist 8-SPT had no effect on AICAR-induced suppression of TNF-alpha, levels. Finally, we observed that AICAR inhibited LPS-induced activation of PI 3-kinase and Akt, whereas it had no effect on the activation of p38 and ERK 1/2. Taken together, these results suggest that the anti-inflammatory action of AICAR in RAW 264.7 macrophages is independent of AMPK activation and is associated with inhibition of LPS-induced activation of PI 3-kinase/Akt pathway. (C) 2004 Elsevier Inc. All rights reserved.