Anti-inflammatory activity of bone morphogenetic protein signaling pathways in stomachs of mice.
Anti-inflammatory activity of bone morphogenetic protein signaling pathways in stomachs of mice.
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DOI：
10.1053/j.gastro.2014.04.015
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发表时间：
2014-08
期刊：
影响因子：
29.4
通讯作者：
Todisco A
中科院分区：
文献类型：
--
作者：
Takabayashi H;Shinohara M;Mao M;Phaosawasdi P;El-Zaatari M;Zhang M;Ji T;Eaton KA;Dang D;Kao J;Todisco A
骨形态发生蛋白（BMP）4是一种调节胃上皮细胞的间充质肽。我们研究了BMP信号通路是否影响细菌感染小鼠后的胃炎症。我们研究了在BMP反应元件控制下表达BMP抑制剂头蛋白或β-半乳糖苷酶基因的转基因小鼠和BMP 4 βgal/+小鼠。通过用幽门螺杆菌或猫螺杆菌感染小鼠来诱导胃炎症。接种后8 ~ 12周，收集胃组织样本，进行免疫组化、定量、逆转录聚合酶链反应和免疫印迹分析。我们使用酶联免疫吸附试验来测量细胞因子水平的培养上清液中的小鼠脾细胞和树突状细胞，以及从人胃上皮细胞（AGS细胞系）。我们还测量了BMP-2，BMP-4，BMP-7和BMP抑制剂LDN-193189对AGS细胞和犬壁细胞和粘液细胞原代培养物白细胞介素（IL）8信使RNA表达的影响。BMP-4对壁细胞和AGS细胞中NFkB活化的影响通过免疫印迹和荧光素酶测定来检查。转基因表达noggin的小鼠增加幽门螺杆菌或猫幽门螺杆菌诱导的炎症和上皮细胞增殖，加速发育不良的发展，并增加信号转导和转录激活因子3和激活诱导的胞苷脱氨酶的表达。BMP-4在表达α-平滑肌肌动蛋白的间充质细胞中表达，并激活胃上皮中的BMP信号通路。在C57 BL/6、BRE-β-半乳糖苷酶或BMP-4βgal/+小鼠的免疫细胞中均未检测到BMP-4表达或BMP信号传导。树突状细胞或脾细胞与BMP-4的孵育不影响脂多糖刺激的细胞因子的产生。BMP-4、BMP-2和BMP-7抑制犬胃上皮细胞基础和肿瘤坏死因子α刺激的IL 8表达。LDN-193189阻止了AGS细胞中BMP 4介导的基础和肿瘤坏死因子α刺激的IL 8表达抑制。BMP-4对TNFα刺激的IκBα的磷酸化和降解或对TNFα诱导的NFκβ报告基因没有影响。BMP信号转导减少了幽门螺杆菌或猫幽门螺杆菌感染小鼠后胃粘膜的炎症并抑制了胃粘膜的发育异常变化。
Bone morphogenetic protein (BMP)4 is a mesenchymal peptide that regulates cells of the gastric epithelium. We investigated whether BMP signaling pathways affect gastric inflammation after bacterial infection of mice. We studied transgenic mice that express either the BMP inhibitor noggin or the β- galactosidase gene under the control of a BMP-responsive element and BMP4βgal/+ mice. Gastric inflammation was induced by infection of mice with either Helicobacter pylori or Helicobacter felis. Eight to 12 weeks after inoculation, gastric tissue samples were collected and immunohistochemical, quantitative, reverse-transcription polymerase chain reaction and immunoblot analyses were performed. We used enzyme-linked immunosorbent assays to measure cytokine levels in supernatants from cultures of mouse splenocytes and dendritic cells, as well as from human gastric epithelial cells (AGS cell line). We also measured the effects of BMP-2, BMP-4, BMP-7, and the BMP inhibitor LDN-193189 on the expression of interleukin (IL)8 messenger RNA by AGS cells and primary cultures of canine parietal and mucus cells. The effect of BMP-4 on NFkB activation in parietal and AGS cells was examined by immunoblot and luciferase assays. Transgenic expression of noggin in mice increased H pylori– or H felis–induced inflammation and epithelial cell proliferation, accelerated the development of dysplasia, and increased expression of the signal transducer and activator of transcription 3 and activation-induced cytidine deaminase. BMP-4 was expressed in mesenchymal cells that expressed α-smooth muscle actin and activated BMP signaling pathways in the gastric epithelium. Neither BMP-4 expression nor BMP signaling were detected in immune cells of C57BL/6, BRE–β-galactosidase, or BMP-4βgal/+ mice. Incubation of dendritic cells or splenocytes with BMP-4 did not affect lipopolysaccharide-stimulated production of cytokines. BMP-4, BMP-2, and BMP-7 inhibited basal and tumor necrosis factor α–stimulated expression of IL8 in canine gastric epithelial cells. LDN-193189 prevented BMP4-mediated inhibition of basal and tumor necrosis factor α–stimulated expression of IL8 in AGS cells. BMP-4 had no effect on TNFα-stimulated phosphorylation and degradation of IκBα, or on TNFα induction of a NFκβ reporter gene. BMP signaling reduces inflammation and inhibits dysplastic changes in the gastric mucosa after infection of mice with H pylori or H felis.
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DOI：
10.1152/ajpgi.00244.2011
发表时间：
2012-05-01
影响因子：
4.5
作者：
Maric, Ivana;Kucic, Natalia;Vukicevic, Slobodan
通讯作者：
Vukicevic, Slobodan
影响因子：
--
作者：
Blank U;Seto ML;Adams DC;Wojchowski DM;Karolak MJ;Oxburgh L
通讯作者：
Oxburgh L
DOI：
10.1152/ajpgi.00187.2006
发表时间：
2006-12-01
影响因子：
4.5
作者：
Goldenring, James R.;Nomura, Sachiyo
通讯作者：
Nomura, Sachiyo
影响因子：
4.7
作者：
Camilo, Vania;Barros, Rita;Almeida, Raquel
通讯作者：
Almeida, Raquel
影响因子：
7.3
作者：
Bleuming, S. A.;Kodach, L. L.;van den Brink, G. R.
通讯作者：
van den Brink, G. R.