Cellular and molecular mechanism of interleukin-1β modulation of Caco-2 intestinal epithelial tight junction barrier.
Cellular and molecular mechanism of interleukin-1β modulation of Caco-2 intestinal epithelial tight junction barrier.
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DOI：
10.1111/j.1582-4934.2010.01065.x
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发表时间：
2011-04
影响因子：
5.3
通讯作者：
Ma TY
中科院分区：
文献类型：
--
作者：
Al-Sadi R;Ye D;Said HM;Ma TY
白介素-1β (IL-1β) 是一种典型的多功能细胞因子，在克罗恩病的肠道炎症和其他肠道炎症中发挥着重要作用。先前的研究表明，IL-1β 会导致体内动物和体外细胞培养模型系统中肠上皮紧密连接 (TJ) 通透性增加。 IL-1β诱导的肠上皮TJ通透性增加被认为是导致肠道炎症的重要致病机制。然而，介导IL-1β调节肠上皮TJ屏障的信号通路和分子过程仍不清楚。在这里，我们发现 IL-1β 诱导的 Caco-2 单层 TJ 通透性增加是通过激活细胞外信号调节激酶 1/2 (ERK1/2) 信号通路介导的，并且抑制 ERK1/2 活性会抑制 IL-1β 诱导的 Caco-2 TJ 通透性增加。 ERK1/2途径的激活引起下游核转录因子Elk-1的激活。激活的Elk-1易位到细胞核，与肌球蛋白轻链激酶（MLCK）启动子区的顺式结合基序结合，触发MLCK基因激活、MLCK mRNA转录和MLCK蛋白合成，并催化MLCK打开肠上皮TJ屏障。这些研究为介导 IL-1β 诱导的肠上皮 TJ 通透性增加的细胞和分子过程提供了新的见解。
Interleukin-1β (IL-1β) is a prototypical multifunctional cytokine that plays an important role in intestinal inflammation of Crohn’s disease and other inflammatory conditions of the gut. Previous studies have shown that IL-1β causes an increase in intestinal epithelial tight junction (TJ) permeability both in in vivo animal and in vitro cell culture model systems. The IL-1β-induced increase in intestinal epithelial TJ permeability has been postulated to be an important pathogenic mechanism contributing to intestinal inflammation. However, the signalling pathways and the molecular processes that mediate the IL-1β modulation of intestinal epithelial TJ barrier remain unclear. Here, we show that the IL-1β-induced increase in Caco-2 monolayer TJ permeability was mediated by activation of extracellular signal-regulated kinases 1/2 (ERK1/2) signalling pathway and that inhibition of ERK1/2 activity inhibits the IL-1β-induced increase in Caco-2 TJ permeability. The activation of ERK1/2 pathway caused a downstream activation of nuclear transcription factor Elk-1. The activated Elk-1 translocated to the nucleus and binds to the cis-binding motif on myosin light chain kinase (MLCK) promoter region, triggering MLCK gene activation, MLCK mRNA transcription and MLCK protein synthesis and MLCK catalysed opening of the intestinal epithelial TJ barrier. These studies provide novel insight into the cellular and molecular processes that mediate the IL-1β-induced increase in intestinal epithelial TJ permeability.
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影响因子：
15.9
作者：
MADARA, JL;STAFFORD, J
通讯作者：
STAFFORD, J
影响因子：
4.8
作者：
Larsen, CM;Wadt, KAW;Mandrup-Poulsen, T
通讯作者：
Mandrup-Poulsen, T
DOI：
10.1152/ajpgi.2000.279.5.g875
发表时间：
2000-11-01
影响因子：
4.5
作者：
Ma, TY;Hoa, NT;Merryfield, M
通讯作者：
Merryfield, M
影响因子：
24.5
作者：
Arrieta, M. C.;Madsen, K.;Doyle, J.;Meddings, J.
通讯作者：
Meddings, J.
DOI：
10.1083/jcb.102.6.2125
发表时间：
1986-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Madara JL;Barenberg D;Carlson S
通讯作者：
Carlson S