Activation of protein tyrosine phosphatase non-receptor type 2 by spermidine exerts anti-inflammatory effects in human THP-1 monocytes and in a mouse model of acute colitis.
Activation of protein tyrosine phosphatase non-receptor type 2 by spermidine exerts anti-inflammatory effects in human THP-1 monocytes and in a mouse model of acute colitis.
复制标题
DOI：
10.1371/journal.pone.0073703
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Scharl M
中科院分区：
文献类型：
--
作者：
Morón B;Spalinger M;Kasper S;Atrott K;Frey-Wagner I;Fried M;McCole DF;Rogler G;Scharl M
亚精胺是一种膳食多胺，能够激活非受体型蛋白酪氨酸磷酸酶2（PTPN2）。由于已知PTPN2是干扰素 -γ（IFN -γ）诱导反应的负调节因子，且免疫细胞的IFN -γ刺激是炎症性肠病（IBD）免疫病理学中的一个关键过程，我们希望探索亚精胺在体外和体内减轻促炎作用的潜力。
人THP -1单核细胞用IFN -γ和/或亚精胺处理。通过蛋白质印迹分析蛋白质表达和磷酸化，通过定量PCR分析细胞因子表达，通过酶联免疫吸附测定（ELISA）分析细胞因子分泌。通过给予葡聚糖硫酸钠（DSS）在小鼠中诱导结肠炎。通过记录体重、结肠镜检查和组织学评估疾病严重程度。
亚精胺增加了THP -1单核细胞中PTPN2的表达和活性，并以PTPN2依赖的方式降低了IFN -γ诱导的信号转导子和转录激活子（STAT）1和3以及p38丝裂原活化蛋白激酶（MAPK）的磷酸化。随后，在亚精胺处理的细胞中，IFN -γ诱导的细胞内细胞黏附分子（ICAM）-1 mRNA、单核细胞趋化蛋白（MCP）-1和白细胞介素（IL）-6的表达/分泌减少。在PTPN2敲低的细胞中不存在后述效应。在患有DSS诱导的结肠炎的小鼠中，亚精胺治疗导致体重减轻改善，黏膜损伤减少，表明疾病严重程度降低。
亚精胺激活PTPN2可改善THP -1细胞中IFN -γ诱导的炎症反应。此外，亚精胺治疗显著降低了DSS诱导的结肠炎小鼠的疾病严重程度；因此，补充亚精胺以及随后的PTPN2激活可能有助于治疗诸如IBD等慢性肠道炎症。
Spermidine is a dietary polyamine that is able to activate protein tyrosine phosphatase non-receptor type 2 (PTPN2). As PTPN2 is known to be a negative regulator of interferon-gamma (IFN-γ)-induced responses, and IFN-γ stimulation of immune cells is a critical process in the immunopathology of inflammatory bowel disease (IBD), we wished to explore the potential of spermidine for reducing pro-inflammatory effects in vitro and in vivo. Human THP-1 monocytes were treated with IFN-γ and/or spermidine. Protein expression and phosphorylation were analyzed by Western blot, cytokine expression by quantitative-PCR, and cytokine secretion by ELISA. Colitis was induced in mice by dextran sodium sulfate (DSS) administration. Disease severity was assessed by recording body weight, colonoscopy and histology. Spermidine increased expression and activity of PTPN2 in THP-1 monocytes and reduced IFN-γ-induced phosphorylation of signal transducer and activator of transcription (STAT) 1 and 3, as well as p38 mitogen-activated protein kinase (MAPK) in a PTPN2 dependent manner. Subsequently, IFN-γ-induced expression/secretion of intracellular cell adhesion molecule (ICAM)-1 mRNA, monocyte chemoattractant protein (MCP)-1, and interleukin (IL)-6 was reduced in spermidine-treated cells. The latter effects were absent in PTPN2-knockdown cells. In mice with DSS-induced colitis, spermidine treatment resulted in ameliorated weight loss and decreased mucosal damage indicating reduced disease severity. Activation of PTPN2 by spermidine ameliorates IFN-γ-induced inflammatory responses in THP-1 cells. Furthermore, spermidine treatment significantly reduces disease severity in mice with DSS-induced colitis; hence, spermidine supplementation and subsequent PTPN2 activation may be helpful in the treatment of chronic intestinal inflammation such as IBD.
登录
查看更多内容
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
3.8
作者：
Mattila, Elina;Marttila, Heidi;Ivaska, Johanna
通讯作者：
Ivaska, Johanna
影响因子：
29.4
作者：
Rugtveit, J;Nilsen, EM;Scott, H
通讯作者：
Scott, H
影响因子：
24.5
作者：
MAHIDA, YR;PATEL, S;JEWELL, DP
通讯作者：
JEWELL, DP