GLP-2 Attenuates LPS-Induced Inflammation in BV-2 Cells by Inhibiting ERK1/2, JNK1/2 and NF-κB Signaling Pathways.
GLP-2 Attenuates LPS-Induced Inflammation in BV-2 Cells by Inhibiting ERK1/2, JNK1/2 and NF-κB Signaling Pathways.
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GLP-2 通过抑制 ERK1/2、JNK1/2 和 NF-kappaB 信号通路减轻 BV-2 细胞中 LPS 诱导的炎症。
DOI：
10.3390/ijms17020190
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发表时间：
2016-02-04
影响因子：
5.6
通讯作者：
Wang W
中科院分区：
文献类型：
--
作者：
Li N;Liu BW;Ren WZ;Liu JX;Li SN;Fu SP;Zeng YL;Xu SY;Yan X;Gao YJ;Liu DF;Wang W
帕金森病（PD）的发病机制通常涉及小胶质细胞的过度激活。过度激活的小胶质细胞可产生多种炎症介质，从而引发过度炎症并最终导致多巴胺能神经元损伤。胰高血糖素样肽-2（GLP-2）在外周中的抗炎作用已得到证实。然而，它还没有在大脑中得到说明。因此，在本研究中，我们的目的是了解GLP-2在小胶质细胞活化中的作用，并阐明其潜在机制。用GLP-2预处理BV-2细胞，然后用脂多糖（LPS）刺激。检测细胞对促炎酶（iNOS和考克斯-2）和促炎细胞因子（IL-1β、IL-6和TNF-α）的反应，并通过Western blotting检测相关信号通路。还检查了GLP-2对小胶质细胞介导的神经毒性的拯救作用。结果显示，GLP-2可显著降低LPS诱导的诱导型一氧化氮合酶（iNOS）、环氧合酶-s（考克斯-2）、IL-1β、IL-6和TNF-α的产生。NF 449阻断Gαs导致BV-2细胞中这种抗炎作用的丧失。信号通路分析表明，GLP-2减少LPS诱导的ERK 1/2、JNK 1/2和p65磷酸化，而对p38磷酸化没有观察到影响。此外，GLP-2可抑制小胶质细胞介导的神经毒性。所有结果表明GLP-2通过共同调节ERK 1/2、JNK 1/2和p65抑制LPS诱导的小胶质细胞活化。
The pathogenesis of Parkinson’s disease (PD) often involves the over-activation of microglia. Over-activated microglia could produce several inflammatory mediators, which trigger excessive inflammation and ultimately cause dopaminergic neuron damage. Anti-inflammatory effects of glucagon-like peptide-2 (GLP-2) in the periphery have been shown. Nonetheless, it has not been illustrated in the brain. Thus, in this study, we aimed to understand the role of GLP-2 in microglia activation and to elucidate the underlying mechanisms. BV-2 cells were pretreated with GLP-2 and then stimulated by lipopolysaccharide (LPS). Cells were assessed for the responses of pro-inflammatory enzymes (iNOS and COX-2) and pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α); the related signaling pathways were evaluated by Western blotting. The rescue effect of GLP-2 on microglia-mediated neurotoxicity was also examined. The results showed that GLP-2 significantly reduced LPS-induced production of inducible nitric oxide synthase (iNOS), cyclooxygenase-s (COX-2), IL-1β, IL-6 and TNF-α. Blocking of Gαs by NF449 resulted in a loss of this anti-inflammatory effect in BV-2 cells. Analyses in signaling pathways demonstrated that GLP-2 reduced LPS-induced phosphorylation of ERK1/2, JNK1/2 and p65, while no effect was observed on p38 phosphorylation. In addition, GLP-2 could suppress microglia-mediated neurotoxicity. All results imply that GLP-2 inhibits LPS-induced microglia activation by collectively regulating ERK1/2, JNK1/2 and p65.