McGee D W, Bamberg T, Vitkus S J, McGhee J R
Department of Biological Sciences, Binghamton University (SUNY), NY 13902-6000, USA.
Immunology. 1995 Sep;86(1):6-11.
Intestinal epithelial cells are known to secrete a variety of cytokines and may play a role in the immune response at the intestinal mucosa. However, the regulatory mechanisms that govern the secretion of these cytokines are largely unknown. In this report, we have focused on the cytokine interactions that regulate interleukin (IL)-6 secretion by the non-transformed rat small intestinal epithelial cell line IEC-6. Tumour necrosis factor-alpha (TNF-alpha) was found to enhance both IL-6 mRNA expression and protein secretion by the IEC-6 cells. Furthermore, TNF-alpha acted in synergy with either transforming growth factor-beta 1 (TGF-beta 1) or IL-1 beta to greatly enhance IEC-6 cell IL-6 secretion. Although the IEC-6 cells are known to produce TGF-beta, autocrine-secreted TGF-beta was found to have no effect on the elevated IL-6 secretion induced by both TNF-alpha plus IL-1 beta. However, the addition of activated TGF-beta 1 to IEC-6 cultures stimulated with both TNF-alpha and IL-1 beta resulted in greatly elevated levels of IL-6 secretion. Therefore, activated TGF-beta 1 can augment IL-6 secretion stimulated by TNF-alpha and IL-1 beta, either alone or in combination, suggesting that intestinal epithelial cell IL-6 secretion may be under the control of a cytokine network at the intestinal mucosa.
已知肠上皮细胞可分泌多种细胞因子，并可能在肠道黏膜的免疫反应中发挥作用。然而，调控这些细胞因子分泌的机制在很大程度上尚不清楚。在本报告中，我们重点研究了调节未转化的大鼠小肠上皮细胞系IEC-6分泌白细胞介素（IL）-6的细胞因子相互作用。发现肿瘤坏死因子-α（TNF-α）可增强IEC-6细胞的IL-6 mRNA表达和蛋白分泌。此外，TNF-α与转化生长因子-β1（TGF-β1）或IL-1β协同作用，可极大地增强IEC-6细胞的IL-6分泌。虽然已知IEC-6细胞可产生TGF-β，但发现自分泌的TGF-β对TNF-α加IL-1β诱导的IL-6分泌升高没有影响。然而，将活化的TGF-β1添加到用TNF-α和IL-1β刺激的IEC-6培养物中，会导致IL-6分泌水平大幅升高。因此，活化的TGF-β1可增强由TNF-α和IL-1β单独或联合刺激引起的IL-6分泌，这表明肠上皮细胞IL-6的分泌可能受肠道黏膜细胞因子网络的控制。
