Role of enteric nerves in immune-mediated changes in protease-activated receptor 2 effects on gut function.
Role of enteric nerves in immune-mediated changes in protease-activated receptor 2 effects on gut function.
复制标题
DOI：
10.1111/j.1365-2982.2010.01557.x
复制
发表时间：
2010-10
影响因子：
3.5
通讯作者：
Zhao A
中科院分区：
文献类型：
--
作者：
Shea-Donohue T;Notari L;Stiltz J;Sun R;Madden KB;Urban JF Jr;Zhao A
蛋白酶激活受体（PAR）在结构细胞和免疫细胞上表达。PAR效应的起始、持续时间和大小的控制与受体表达水平、蛋白酶的可用性和细胞内信号转导机制有关。我们研究了线虫感染诱导的PAR 2表达变化以及对平滑肌和上皮对PAR 2激动剂反应的影响。在野生型和IL-4、IL-13或STAT 6基因缺陷型小鼠中，在用载体、巴西日本圆线虫或多脑Heligmosomoides或IL-13处理后，评估平滑肌和上皮细胞功能。用河豚毒素阻断肠神经传导，确定肠神经的作用。采用实时荧光定量PCR、免疫印迹和免疫组化检测PAR 2的表达。线虫感染诱导PAR 2 mRNA表达的STAT 6和IL-13依赖性上调。感染诱导的对PAR 2激动剂的过度收缩需要STAT 6/IL-13，并且是神经介导的。与此相反，感染诱导的减少上皮分泌PAR 2激动剂部分依赖于STAT 6和肠神经的独立。分泌不足与上皮细胞顶端表面PAR 2免疫荧光染色减少有关，但与固有层PAR 2免疫荧光染色增强有关。这是第一项研究，以证明免疫调节PAR 2的表达，影响平滑肌和上皮细胞对PAR 2激动剂的反应。平滑肌和上皮细胞之间的反应差异与肠神经的贡献有关。这些数据提供了一种机制，通过该机制，基于免疫的病理学中PAR 2的激活可以诱导肠道功能的短暂和持久变化。
Protease activated receptors (PARs) are expressed on structural and immune cells. Control of initiation, duration, and magnitude of PAR effects is linked to the level of receptor expression, availability of proteases, and the intracellular signal transduction machinery. We investigated nematode infection-induced changes in PAR2 expression and the impact on smooth muscle and epithelial responses to PAR2 agonists. Smooth muscle and epithelial cell function were assessed in wild type, and IL-4, IL-13 or STAT6 gene-deficient mice following treatment with vehicle, Nippostrongylus brasiliensis or Heligmosomoides polygyrus, or IL-13. The role of enteric nerves was determined using tetrodotoxin to block nerve conduction. Expression of PAR2 was assessed by real-time PCR, western blot and immunohistochemistry. Nematode infection induced a STAT6- and IL-13-dependent up-regulation of PAR2 mRNA expression. The infection-induced hypercontractility to PAR2 agonists required STAT6/IL-13 and was neurally-mediated. In contrast, the infection-induced decrease in epithelial secretion to PAR2 agonists was partly dependent on STAT6 and independent of enteric nerves. The hyposecretion was correlated with decreased PAR2 immunofluorescent staining on the apical surface of epithelial cells, but enhanced lamina propria immunostaining for PAR2. This is the first study to demonstrate an immune regulation of PAR2 expression that impacts both smooth muscle and epithelial cell responses to PAR2 agonists. Differences in responses between smooth muscle and epithelial cells are related to the contribution of enteric nerves. These data provide a mechanism by which activation of PAR2 in immune-based pathologies can induce both transient and long-lasting changes in gut function.
登录
查看更多内容
影响因子：
2.1
作者：
Hollenberg, MD;Saifeddine, M;Kawabata, A
通讯作者：
Kawabata, A
影响因子：
20.3
作者：
Colognato, R;Slupsky, JR;Simmet, T
通讯作者：
Simmet, T
影响因子：
29.4
作者：
Barbara, Giovanni;Wang, Bingxian;Corinaldesi, Roberto
通讯作者：
Corinaldesi, Roberto
影响因子：
4.8
作者：
Jacob, C;Yang, PC;Bunnett, NW
通讯作者：
Bunnett, NW
影响因子：
6
作者：
Cenac, N;Coelho, AM;Vergnolle, N
通讯作者：
Vergnolle, N