Dicay Michael S, Hirota Christina L, Ronaghan Natalie J, Peplowski Michael A, Zaheer Raza S, Carati Colin A, MacNaughton Wallace K
Inflammation Research Network and Department of Physiology and Pharmacology, University of Calgary, Calgary, Canada.
Department of Anatomy and Histology, Flinders University, Bedford Park, Australia.
PLoS One. 2015 Mar 20;10(3):e0118713. doi: 10.1371/journal.pone.0118713. eCollection 2015.
Inflammatory bowel diseases are associated with dysregulated electrolyte and water transport and resultant diarrhea. Aquaporins are transmembrane proteins that function as water channels in intestinal epithelial cells. We investigated the effect of the inflammatory cytokine, interferon-γ, which is a major player in inflammatory bowel diseases, on aquaporin-1 expression in a mouse colonic epithelial cell line, CMT93. CMT93 monolayers were exposed to 10 ng/mL interferon-γ and aquaporin-1 mRNA and protein expressions were measured by real-time PCR and western blot, respectively. In other experiments, CMT93 cells were pretreated with inhibitors or were transfected with siRNA to block the effects of Janus kinases, STATs 1 and 3, or interferon regulatory factor 2, prior to treatment with interferon-γ. Interferon-γ decreased aquaporin-1 expression in mouse intestinal epithelial cells in a manner that did not depend on the classical STAT1/JAK2/IRF-1 pathway, but rather, on an alternate Janus kinase (likely JAK1) as well as on STAT3. The pro-inflammatory cytokine, interferon-γ may contribute to diarrhea associated with intestinal inflammation in part through regulation of the epithelial aquaporin-1 water channel via a non-classical JAK/STAT receptor signalling pathway.
炎症性肠病与电解质和水转运失调以及由此导致的腹泻有关。水通道蛋白是在肠道上皮细胞中作为水通道发挥作用的跨膜蛋白。我们研究了炎症性细胞因子γ干扰素（它是炎症性肠病中的主要参与者）对小鼠结肠上皮细胞系CMT93中水通道蛋白-1表达的影响。将CMT93单层细胞暴露于10 ng/mL的γ干扰素中，分别通过实时PCR和蛋白质印迹法检测水通道蛋白-1的mRNA和蛋白质表达。在其他实验中，在使用γ干扰素处理之前，用抑制剂预处理CMT93细胞或用小干扰RNA转染以阻断Janus激酶、信号转导和转录激活因子1和3或干扰素调节因子2的作用。γ干扰素以不依赖于经典的信号转导和转录激活因子1/Janus激酶2/干扰素调节因子1途径，而是依赖于另一种Janus激酶（可能是Janus激酶1）以及信号转导和转录激活因子3的方式降低小鼠肠道上皮细胞中水通道蛋白-1的表达。促炎细胞因子γ干扰素可能部分通过非经典的Janus激酶/信号转导和转录激活因子受体信号通路调节上皮水通道蛋白-1水通道，从而导致与肠道炎症相关的腹泻。
