Increased susceptibility to dextran sulfate sodium induced colitis in the T cell protein tyrosine phosphatase heterozygous mouse.
Increased susceptibility to dextran sulfate sodium induced colitis in the T cell protein tyrosine phosphatase heterozygous mouse.
复制标题
DOI：
10.1371/journal.pone.0008868
复制
发表时间：
2010-01-25
期刊：
影响因子：
3.7
通讯作者：
Tremblay ML
中科院分区：
文献类型：
--
作者：
Hassan SW;Doody KM;Hardy S;Uetani N;Cournoyer D;Tremblay ML
T细胞蛋白酪氨酸磷酸酶（TC - PTP / PTPN2）是一种对免疫系统正常功能至关重要的酶，它参与细胞增殖和炎症的控制。我们先前观察到TC - PTP - / - 小鼠表现出多种免疫缺陷，对脂多糖（LPS）过敏，并且由于贫血和广泛的炎症在出生三周内死亡。2007年报道的对威康信托病例对照协会（WTCC）全基因组扫描数据的一项近期分析表明，TC - PTP在炎症性肠病（IBD）中具有潜在作用。为了进一步研究TC - PTP在IBD中的潜在作用，我们研究了饮用含葡聚糖硫酸钠（DSS）水的杂合TC - PTP突变小鼠。与对照动物相比，我们观察到经DSS处理的TC - PTP + / - 小鼠的结肠黏膜、结肠与体重的比例有显著变化，以及白细胞介素 - 6（IL - 6）、白细胞介素 - 23（IL - 23）、白细胞介素 - 12β（1L - 12β）、干扰素 - γ（IFN - γ）、肿瘤坏死因子 - α（TNF - α）的信使核糖核酸（mRNA）转录本上调。此外，经DSS处理的TC - PTP + / - 小鼠血清中IL - 6水平的上调证实，具有单拷贝TC - PTP基因的小鼠由于DSS刺激导致的肠上皮侵蚀而对全身性炎症表现出更高的易感性。我们的研究结果支持在类似IBD病情的发展过程中，PTPN2对Janus激酶1和3（Jak1，Jak3）以及下游信号转导和转录激活因子1、3和5（Stat1，Stat3，Stat5）缺乏调节作用。病理和分子分析表明，TC - PTP的缺乏导致杂合TC - PTP + / - 小鼠肠道出现促炎状况。这些关于TC - PTP半缺失的新发现支持了TC - PTP是炎症细胞因子信号传导的重要调节因子且可能与IBD的病理生理学有关的假说。
T cell protein tyrosine phosphatase (TC-PTP / PTPN2) is an enzyme that is essential for the proper functioning of the immune system and that participates in the control of cell proliferation, and inflammation. We previously observed that TC-PTP−/− mice display various immunodeficiencies, hypersensitivity to LPS and die within three weeks of birth due to anemia and widespread inflammation. A recent analysis of the Wellcome Trust Case Control Consortium (WTCC) genome wide scan data, reported in 2007, indicated a potential role for TC-PTP in inflammatory bowel disease (IBD). To further investigate the potential role of TC-PTP in IBD, we studied heterozygous TC-PTP mutant mice challenged with dextran sulfate sodium (DSS) in their drinking water. In comparison to control animals, we observed significant changes in the colon mucosa of DSS-treated TC-PTP+/− mice, in the ratio of colon to body weight, as well as an up-regulation of mRNA transcripts for IL-6, IL-23, 1L-12β, IFN-γ, TNF-α. Moreover, up-regulation of serum IL-6 levels in DSS-treated TC-PTP+/− mice confirms that mice with a single copy of the TC-PTP gene display increased susceptibility to systemic inflammation due to bowel epithelial erosion resulting from DSS challenge. Our findings support the lack of modulation of Janus kinases 1 and 3 (Jak1, Jak3), and the downstream signal transducer and activator of transcription 1,3 and 5 (Stat1, Stat3, Stat 5) by PTPN2 in the development of IBD like condition. Pathological and molecular analysis reveal that the deficiency of TC-PTP results in pro-inflammatory condition in the bowel of heterozygous TC-PTP+/− mice. These novel findings in TC-PTP hemi-deficiency support the hypothesis that TC-PTP is an important regulator of inflammatory cytokine signaling and that it may be implicated in the pathophysiology of IBD.
登录
查看更多内容
影响因子：
3.1
作者：
Fitzpatrick, LR;Wang, J;Le, T
通讯作者：
Le, T
影响因子：
3.7
作者：
Franke A;Hampe J;Rosenstiel P;Becker C;Wagner F;Häsler R;Little RD;Huse K;Ruether A;Balschun T;Wittig M;Elsharawy A;Mayr G;Albrecht M;Prescott NJ;Onnie CM;Fournier H;Keith T;Radelof U;Platzer M;Mathew CG;Stoll M;Krawczak M;Nürnberg P;Schreiber S
通讯作者：
Schreiber S
影响因子：
3.9
作者：
Masubuchi, Y;Horie, T
通讯作者：
Horie, T
影响因子：
29.4
作者：
Wu, Feng;Zikusoka, Michelle;Kwon, John H.
通讯作者：
Kwon, John H.
影响因子：
168.9
作者：
Shanahan, F
通讯作者：
Shanahan, F