Targeting AMCase reduces esophageal eosinophilic inflammation and remodeling in a mouse model of egg induced eosinophilic esophagitis.
Targeting AMCase reduces esophageal eosinophilic inflammation and remodeling in a mouse model of egg induced eosinophilic esophagitis.
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DOI：
10.1016/j.intimp.2013.10.026
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发表时间：
2014-01
影响因子：
5.6
通讯作者：
Broide DH
中科院分区：
文献类型：
--
作者：
Cho JY;Rosenthal P;Miller M;Pham A;Aceves S;Sakuda S;Broide DH
在小鼠肺嗜酸性炎症模型中抑制AMCase的研究产生了相互矛盾的结果，一些研究表明抑制了嗜酸性炎症，而另一些研究则没有。还没有研究探讨AMCase抑制在嗜酸性食管炎(EoE)中的作用。我们使用卵子(OVA)诱导的EoE的小鼠模型，以确定药物抑制AMCase是否减少EoE中的嗜酸性炎症和食道重塑。BALB/c小鼠食道内注射OVA 6周后，可诱导食道嗜酸性粒细胞和肥大细胞水平增加，并出现食道重塑(纤维化、基底带增生、细胞外基质蛋白纤维粘连蛋白沉积)的特征。BALB/c小鼠腹腔注射异丙三胺显著抑制食道AMCase的活性。Ip allsamidin对AMCase的药理抑制既能抑制OVA诱导的食管嗜酸性炎症的增加，又能抑制OVA诱导的食道重塑(纤维化、上皮基底带增生、纤维连接蛋白的细胞外基质沉积)。Ip allsamidin抑制食道中的嗜酸性炎症与减少食道中的嗜酸性粒细胞趋化因子-1的表达有关。口服别沙米丁可抑制上皮嗜酸性炎症，但不能抑制食道重塑。这些研究表明，AMCase的药理抑制导致抑制EoE小鼠模型中的嗜酸性炎症和食道重塑，部分是通过减少与EoE发病有关的趋化因子(即eoaxin-1)的作用实现的。
Studies of AMCase inhibition in mouse models of lung eosinophilic inflammation have produced conflicting results with some studies demonstrating inhibition of eosinophilic inflammation and others not. No studies have investigated the role of AMCase inhibition in eosinophilic esophagitis (EoE). We have used a mouse model of egg (OVA) induced EoE to determine whether pharmacologic inhibition of AMCase with allosamidin reduced eosinophilic inflammation and remodeling in the esophagus in EoE. Administration of intra-esophageal OVA for 6 weeks to BALB/c mice induced increased levels of esophageal eosinophils, mast cells, and features of esophageal remodeling (fibrosis, basal zone hyperplasia, deposition of the extracellular matrix protein fibronectin). Administration of intraperitoneal (ip) allosamidin to BALB/c mice significantly inhibited AMCase enzymatic activity in the esophagus. Pharmacologic inhibition of AMCase with ip allosamidin inhibited both OVA induced increases in esophageal eosinophilic inflammation and OVA induced esophageal remodeling (fibrosis, epithelial basal zone hyperplasia, extracellular matrix deposition of fibronectin). This inhibition of eosinophilic inflammation in the esophagus by ip allosamidin was associated with reduced eotaxin-1 expression in the esophagus. Oral allosamidin inhibited eosinophilic inflammation in the epithelium but did not inhibit esophageal remodeling. These studies suggest that pharmacologic inhibition of AMCase results in inhibition of eosinophilic inflammation and remodeling in the esophagus in a mouse model of egg induced EoE partially through effects in the esophagus on reducing chemokines (i.e. eotaxin-1) implicated in the pathogenesis of EoE.
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DOI：
10.1097/aci.0b013e3283306533
发表时间：
2009-10
影响因子：
2.8
作者：
Ober C;Chupp GL
通讯作者：
Chupp GL
DOI：
10.1016/j.bbrc.2009.09.075
发表时间：
2009-12-04
影响因子：
3.1
作者：
Matsumoto, Takafumi;Inoue, Hiromasa;Nakanishi, Yoichi
通讯作者：
Nakanishi, Yoichi
影响因子：
4.8
作者：
Rao, FV;Houston, DR;van Aalten, DMF
通讯作者：
van Aalten, DMF
DOI：
10.1038/nsb0296-133
发表时间：
1996-02-01
期刊：
NATURE STRUCTURAL BIOLOGY
影响因子：
--
作者：
Monzingo, AF;Marcotte, EM;Robertus, JD
通讯作者：
Robertus, JD
DOI：
10.2183/pjab.77.79
发表时间：
2001-05-01
影响因子：
3.1
作者：
Nakanishi, E;Okamoto, S;Sakuda, S
通讯作者：
Sakuda, S