Ecrg4 attenuates the inflammatory proliferative response of mucosal epithelial cells to infection.
Ecrg4 attenuates the inflammatory proliferative response of mucosal epithelial cells to infection.
复制标题
DOI：
10.1371/journal.pone.0061394
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Baird A
中科院分区：
文献类型：
--
作者：
Kurabi A;Pak K;Dang X;Coimbra R;Eliceiri BP;Ryan AF;Baird A
我们报告了孤儿候选肿瘤抑制基因食管癌相关基因4（Ecrg 4）的表达与中耳（ME）粘膜上皮细胞对感染的反应之间的负相关关系。首先，我们发现组成型Ecrg4 mRNA表达在正常，静止ME粘膜，粘膜上皮细胞的免疫染色和免疫印迹的14 kDa Ecrg4蛋白的组织裂解物证实。实验ME感染后，Ecrg4基因表达迅速下降超过80%，3至48小时之间，感染后。当将这种感染的粘膜的外植体置于培养物中并用编码Ecrg4基因的腺病毒（AD）（ADECrg4）转导时，粘膜细胞的增殖和迁移反应被显著抑制。ADEcrg4转导对照外植体从未感染的ME没有影响的基础生长和迁移。通过在感染前48小时预注射具有ADEcrg4的ME，体内Ecrg4的过表达防止了Ecrg4的自然下调，减少了粘膜增殖并防止了通常在感染后观察到的炎性细胞浸润。总之，这些数据支持Ecrg4在协调粘膜上皮感染的炎症和增殖反应中起作用的假设，这表明其推定的抗肿瘤活性的可能机制。
We report an inverse relationship between expression of the orphan candidate tumor suppressor gene esophageal cancer related gene 4 (Ecrg4), and the mucosal epithelial cell response to infection in the middle ear (ME). First, we found constitutive Ecrg4 mRNA expression in normal, quiescent ME mucosa that was confirmed by immunostainning of mucosal epithelial cells and immunoblotting of tissue lysates for the 14 kDa Ecrg4 protein. Upon experimental ME infection, Ecrg4 gene expression rapidly decreased by over 80%, between 3 to 48 hrs, post infection. When explants of this infected mucosa were placed in culture and transduced with an adenovirus (AD) encoding Ecrg4 gene (ADEcrg4), the proliferative and migratory responses of mucosal cells were significantly inhibited. ADEcrg4 transduction of control explants from uninfected MEs had no effect on basal growth and migration. Over-expression of Ecrg4 in vivo, by pre-injecting MEs with ADEcrg4 48 hrs prior to infection, prevented the natural down-regulation of Ecrg4, reduced mucosal proliferation and prevented inflammatory cell infiltration normally observed after infection. Taken together, these data support a hypothesis that Ecrg4 plays a role in coordinating the inflammatory and proliferative response to infection of mucosal epithelium suggesting a possible mechanism for its putative anti-tumor activity.
登录
查看更多内容
影响因子：
8
作者：
通讯作者：
--
影响因子：
6.4
作者：
Li, Lin-Wei;Yu, Xi-Ying;Lu, Shih-Hsin
通讯作者：
Lu, Shih-Hsin
影响因子：
15.9
作者：
Kagnoff, MF;Eckmann, L
通讯作者：
Eckmann, L
DOI：
10.1126/science.1183021
发表时间：
2010-01-15
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Iwasaki A;Medzhitov R
通讯作者：
Medzhitov R
影响因子：
14.2
作者：
Ebmeyer, J;Furukawa, M;Wasserman, S
通讯作者：
Wasserman, S