Dignass A U, Podolsky D K
Gastrointestinal Unit, Department of Medicine, Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, 02114, USA.
Exp Cell Res. 1996 Jun 15;225(2):422-9. doi: 10.1006/excr.1996.0193.
Although interleukin 2 (IL-2) has been presumed to have a highly circumscribed range of target cells limited largely to classic immune cell populations, the presence of functional IL-2 receptors in rat epithelial cell lines has recently been demonstrated. Limited information is available about the functional effects of IL-2 on intestinal epithelial cells. The effect of recombinant IL-2 on intestinal epithelial cell migration was assessed using a previously described in vitro model of epithelial restitution by quantitation of cells migrating into standard wounds established in confluent IEC-6 cell monolayers. Transforming growth factor beta content was assessed by Northern blot and bioassay. Exogenous IL-2 enhanced epithelial cell restitution in vitro on average 3.8-fold; this effect was independent of cell proliferation. Enhancement of restitution through IL-2 could be completely blocked through antibodies directed against TGFbeta1 and interleukin-2 receptor, indicating that stimulation of epithelial cell restitution is specifically enhanced by interleukin-2 and mediated through a TGFbeta-dependent pathway. In addition, increased expression of TGFbeta1 mRNA and increased levels of bioactive TGFbeta peptide in wounded monolayers treated with IL-2 compared to unwounded monolayers cultured in serum-deprived medium alone support the notion that enhancement of epithelial cell restitution in vitro is mediated through a TGFbeta-dependent pathway. These studies suggest that IL-2, a potent cytokine whose biological origin and targets have been presumed to be largely limited to lymphocyte and macrophage populations, may play a role in preserving the integrity of the intestinal epithelium following various forms of injuries.
尽管白细胞介素2（IL-2）被认为作用靶细胞范围非常有限，主要局限于经典免疫细胞群体，但最近已证实在大鼠上皮细胞系中存在功能性IL-2受体。关于IL-2对肠上皮细胞的功能作用的信息有限。使用先前描述的上皮修复体外模型，通过对迁移到汇合的IEC-6细胞单层中形成的标准伤口中的细胞进行定量，评估重组IL-2对肠上皮细胞迁移的影响。通过Northern印迹和生物测定法评估转化生长因子β含量。外源性IL-2在体外平均增强上皮细胞修复3.8倍；这种作用与细胞增殖无关。通过IL-2增强修复作用可被针对TGFβ1和白细胞介素-2受体的抗体完全阻断，表明白细胞介素-2特异性增强上皮细胞修复作用，并通过TGFβ依赖性途径介导。此外，与仅在无血清培养基中培养的未受伤单层相比，用IL-2处理的受伤单层中TGFβ1 mRNA表达增加和生物活性TGFβ肽水平升高，支持体外上皮细胞修复增强是通过TGFβ依赖性途径介导的观点。这些研究表明，IL-2作为一种强效细胞因子，其生物学来源和靶细胞曾被认为主要局限于淋巴细胞和巨噬细胞群体，可能在各种形式的损伤后维持肠上皮的完整性中发挥作用。
