GLP-2 Suppresses LPS-Induced Inflammation in Macrophages by Inhibiting ERK Phosphorylation and NF-κB Activation
GLP-2 Suppresses LPS-Induced Inflammation in Macrophages by Inhibiting ERK Phosphorylation and NF-κB Activation
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DOI：
10.1159/000363025
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发表时间：
2014-01-01
影响因子：
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通讯作者：
Liu, Dianfeng
中科院分区：
文献类型：
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作者：
Xie, Shanshan;Liu, Bingrun;Liu, Dianfeng
背景/目的：GLP-2已被证明具有抗炎作用，但其潜在的分子机制尚不明确。由于巨噬细胞在炎症的发生和维持中起重要作用，我们研究了外源性GLP-2是否调节LPS刺激小鼠腹膜巨噬细胞中促炎蛋白的表达。方法：用不同浓度的GLP-2预处理巨噬细胞1 h，然后用LPS刺激。采用Western blotting、ELISA和qRT-PCR分析其对促炎酶（iNOS、COX-2）和促炎因子（tnf - α、IL-1 β、IL-6）的影响。我们还研究了NF-kappa B或MARK信号是否参与GLP-2的作用。结果：在巨噬细胞中，GLP-2减弱了LPS对iNOS、COX-2、tnf - α、IL-1 β和IL-6蛋白和mRNA表达水平的影响。用GLP-2孵育巨噬细胞也能减弱lps诱导的I κ B- α降解、I κ B- α磷酸化和nf - κ B易位。在GLP-2存在的情况下，LPS处理对ERK磷酸化的影响也被大大减弱。然而，GLP-2并没有显著改变LPS对p38和JNK活性的影响。结论：这些发现表明，在LPS引发的巨噬细胞中，GLP-2通过抑制NE-kappa B活性和ERK磷酸化的机制减少了促炎酶和细胞因子的产生。巴塞尔S. Karger股份有限公司版权所有
Background/Aims: GLP-2 has been shown to exert anti-inflammatory effects, but the underlying molecular mechanisms remained undefined. As macrophages are important in the development and maintenance of inflammation, we investigated whether exogenous GLP-2 modulates the expression of pro-inflammatory proteins in LPS stimulated murine peritoneal macrophages. Methods: Macrophages were pretreated with various concentrations of GLP-2 for 1 h and then stimulated with LPS. The effects on pro-inflammatory enzymes (iNOS and COX-2), and pro-inflammatory cytokines (TNF-alpha, IL-1 beta and IL-6) were analysed by Western blotting, ELISA and qRT-PCR. We also examined whether NF-kappa B or MARK signaling was involved in the effects of GLP-2. Results: In macrophages, GLP-2 blunted the effect of LPS on protein and mRNA expression levels of iNOS, COX-2, TNF-alpha, IL-1 beta and IL-6. Eke-incubation of macrophages with GLP-2 also blunted LPS-induced I kappa B-alpha degradation, I kappa B-alpha phosphorylation and NF-kappa B translocation. In the presence of GLP-2, the effect of LPS treatment on ERK phosphorylation was also profoundly blunted. GLP-2 did, however, not significantly modify the effects of LPS on p38 and JNK activities. Conclusions: These findings demonstrate that in LPS primed macrophages, GLP-2 reduced pro-inflammatory enzymes and cytokine production via mechanisms involving the suppression of NE-kappa B activity and ERK phosphorylation. Copyright (C) 2014 S. Karger AG, Basel