The Attenuation of 14-3-3ζ is Involved in the Caffeic Acid-Blocked Lipopolysaccharide-Stimulated Inflammatory Response in RAW264.7 Macrophages
The Attenuation of 14-3-3ζ is Involved in the Caffeic Acid-Blocked Lipopolysaccharide-Stimulated Inflammatory Response in RAW264.7 Macrophages
复制标题
14-3-3γ 的衰减参与 RAW264.7 巨噬细胞中咖啡酸封闭的脂多糖刺激的炎症反应
DOI：
10.1007/s10753-017-0618-1
复制
发表时间：
2017-10-01
期刊：
影响因子：
5.1
通讯作者：
Chu, Zhiping
中科院分区：
文献类型：
--
作者：
Lu, Ming;Dai, Yi;Chu, Zhiping
炎症在许多疾病的发生和发展中起着重要作用。咖啡酸（CaA）是一种天然存在的羟基肉桂酸衍生物，具有低毒性和抗炎等多种生物学功能。CaA抑制炎症反应的分子机制非常复杂，通常，下调这些重要转录因子的磷酸化，例如核因子κB（NF-κB）和信号转导和转录激活因子-3（STAT-3），发挥重要作用。在这里，我们发现，在RAW264.7巨噬细胞，钙拮抗脂多糖（LPS）刺激的炎症反应，通过减弱14-3-3 β（磷酸化蛋白调节剂）的表达。简而言之，14-3-3 β的表达增加涉及LPS诱导的炎症反应。CaA通过抑制LPS诱导的肿瘤坏死因子-α（TNF-α）分泌和增强14 - 3 -3 β泛素化而阻断LPS诱导的14 - 3 - 3 β泛素化。这些过程抑制LPS诱导的NF-κB和STAT-3的活化（磷酸化），进而阻断诱导型NO合酶（iNOS）、白细胞介素-6（IL-6）和TNF-α的转录活化，并最终减弱一氧化氮（NO）、IL-6和TNF-α的产生。通过了解CaA抑制14-3-3 β的新机制，我们的研究扩展了对CaA诱导的抗炎潜力所涉及的分子机制的理解。
Inflammation plays important roles in the initiation and progress of many diseases. Caffeic acid (CaA) is a naturally occurring hydroxycinnamic acid derivative, which shows hypotoxicity and diverse biological functions, including anti-inflammation. The molecular mechanisms involved in the CaA-inhibited inflammatory response are very complex; generally, the down-regulated phosphorylation of such important transcriptional factors, for example, nuclear factor κB (NF-κB) and signal transducers and activators of transcription-3 (STAT-3), plays an important role. Here, we found that in RAW264.7 macrophage cells, CaA blocked lipopolysaccharide (LPS)-stimulated inflammatory response by attenuating the expression of 14-3-3ζ (a phosphorylated protein regulator). Briefly, the increased expression of 14-3-3ζ was involved in the LPS-induced inflammatory response. CaA blocked the LPS-elevated 14-3-3ζ via attenuating the LPS-induced tumor necrosis factor-α (TNF-α) secretion and via enhancing the 14-3-3ζ ubiquitination. These processes inhibited the LPS-induced activation (phosphorylation) of NF-κB and STAT-3, in turn blocked the transcriptional activation of inducible NO synthase (iNOS), interleukin-6 (IL-6), and TNF-α, and finally attenuated the productions of nitric oxide (NO), IL-6, and TNF-α. By understanding a novel mechanism whereby CaA inhibited the 14-3-3ζ, our study expanded the understanding of the molecular mechanisms involved in the anti-inflammation potential induced by CaA.