Ruemmele F M, Gurbindo C, Mansour A M, Marchand R, Levy E, Seidman E G
Hôpital Sainte-Justine, Department of Pediatrics, Faculty of Medicine, University of Montreal, Quebec, Canada.
J Cell Physiol. 1998 Jul;176(1):120-6. doi: 10.1002/(SICI)1097-4652(199807)176:1<120::AID-JCP14>3.0.CO;2-B.
Intestinal epithelial cells and the mucosal immune cells in close proximity are thought to interact very closely. One well-established mechanism of this intercellular cross-talk is via the production of cytokines such as interferon gamma (IFNgamma). The aim of this study was to analyze the effects of IFNgamma on intestinal crypt epithelial cells. IEC-6 cells were cultured in the presence or absence of IFNgamma to measure its effects on proliferation, cell cycle, apoptosis, and major histocompatibility complex (MHC) class II antigen expression. Even at very low doses (0.01 U/ml), IFNgamma significantly inhibited IEC-6 cell proliferation, as demonstrated by reduced 3H-thymidine uptake, stable cell count, and complete arrest in the quiescent G0/G1 phase of the cell cycle. Incubation with supraphysiological doses of IFNgamma (100-1,000 U/ml) did not induce apoptosis, as assessed by morphology and the TUNEL assay. IFNgamma significantly induced de novo IEC-6 class II antigen expression. Tumor necrosis factor alpha (TNF alpha), which alone had no effect, synergistically enhanced this effect of IFNgamma. MHC class II antigen expression was observed to be independent of cell cycle phase. Our results indicate that IFNgamma alters immature crypt epithelial cell turnover and upregulates MHC class II expression. These alterations may be important in the pathogenesis of immune-mediated bowel disorders.
人们认为，肠道上皮细胞与紧邻的黏膜免疫细胞之间存在非常紧密的相互作用。这种细胞间相互交流的一种公认机制是通过产生细胞因子，如γ干扰素（IFNγ）。本研究的目的是分析IFNγ对肠道隐窝上皮细胞的影响。在有或没有IFNγ的情况下培养IEC-6细胞，以测量其对细胞增殖、细胞周期、细胞凋亡和主要组织相容性复合体（MHC）II类抗原表达的影响。即使在非常低的剂量（0.01 U/ml）下，IFNγ也能显著抑制IEC-6细胞增殖，3H-胸苷摄取减少、细胞计数稳定以及细胞周期静止的G0/G1期完全停滞均证明了这一点。用超生理剂量的IFNγ（100 - 1000 U/ml）孵育并未诱导细胞凋亡，通过形态学和TUNEL检测评估均是如此。IFNγ能显著诱导IEC-6细胞II类抗原的从头表达。单独使用时无作用的肿瘤坏死因子α（TNFα）能协同增强IFNγ的这一作用。观察到MHC II类抗原表达与细胞周期阶段无关。我们的结果表明，IFNγ改变未成熟隐窝上皮细胞的更新并上调MHC II类表达。这些改变可能在免疫介导的肠道疾病发病机制中具有重要意义。
