Hoffmann Peter, Sturm Andreas, Stein Jürgen, Dignass Axel U
Department of Internal Medicine I, Kliniken Essen Mitte, Germany.
Regul Pept. 2011 Jun 7;168(1-3):27-31. doi: 10.1016/j.regpep.2011.02.013. Epub 2011 Mar 5.
Interferon γ (IFNγ) has been originally identified by its anti-viral activity and has been demonstrated to act as potent modulator of the immune system with a range of target cells limited largely to immune cell populations. Although IFNγ has been shown to directly affect the barrier function of intestinal epithelial cells, only limited information is available about other functional effects of IFNγ on intestinal epithelial cells.
The effects on intestinal epithelial cell migration were studied using a previously described in-vitro model of epithelial restitution in confluent IEC-6 cell monolayers. Intestinal epithelial cell proliferation rates were assessed in various human and rat intestinal and colon epithelial cell lines using colorimetric MTT assays. Apoptosis of IEC-6 cells exposed to IFNγ was assessed by flow cytometry. In addition, transforming growth factor β mRNA expression after IFNγ treatment of IEC-6 cells was assessed by Northern blot analysis.
IFNγ significantly stimulated intestinal epithelial cell migration in an in-vitro wounding model. Furthermore, IFNγ caused a significant dose-dependent inhibition of epithelial cell proliferation in non-transformed small intestinal IEC-6 cells and human colon cancer-derived HT-29 cells and no significant rates of apoptosis were detected in the exposed epithelial cells. The effect of IFNγ on epithelial cell migration and proliferation could be completely blocked by neutralizing antibodies against TGFβ indicating that these effects are mediated through a TGFβ dependent pathway. In addition, increased expression of TGFβ1 mRNA by IEC-6 cells after treatment with IFNγ supports the hypothesis that IFNγ modulates intestinal epithelial cell function through a TGFβ-dependent pathway.
These studies suggest that IFNγ produced by constituents of the mucosal immune system modulates epithelial cell functions with relevance for intestinal wound healing and may play a role in preserving the integrity of the intestinal epithelium following various forms of injuries.
干扰素γ（IFNγ）最初因其抗病毒活性而被发现，现已证明它是免疫系统的强效调节剂，其靶细胞范围主要限于免疫细胞群体。尽管已表明IFNγ可直接影响肠道上皮细胞的屏障功能，但关于IFNγ对肠道上皮细胞的其他功能作用的信息却十分有限。
使用先前描述的汇合IEC - 6细胞单层上皮修复体外模型研究对肠道上皮细胞迁移的影响。使用比色MTT法评估各种人和大鼠肠道及结肠上皮细胞系中的肠道上皮细胞增殖率。通过流式细胞术评估暴露于IFNγ的IEC - 6细胞的凋亡情况。此外，通过Northern印迹分析评估IFNγ处理IEC - 6细胞后转化生长因子β mRNA的表达。
在体外创伤模型中，IFNγ显著刺激肠道上皮细胞迁移。此外，IFNγ对未转化的小肠IEC - 6细胞和人结肠癌衍生的HT - 29细胞中的上皮细胞增殖产生显著的剂量依赖性抑制，并且在暴露的上皮细胞中未检测到明显的凋亡率。针对TGFβ的中和抗体可完全阻断IFNγ对上皮细胞迁移和增殖的作用，表明这些作用是通过TGFβ依赖性途径介导的。此外，IFNγ处理后IEC - 6细胞中TGFβ1 mRNA表达增加，支持了IFNγ通过TGFβ依赖性途径调节肠道上皮细胞功能的假说。
这些研究表明，黏膜免疫系统成分产生的IFNγ调节与肠道伤口愈合相关的上皮细胞功能，并可能在各种形式的损伤后维持肠道上皮的完整性中发挥作用。
