Kondo Mitsuko, Tamaoki Jun, Takeyama Kiyoshi, Nakata Junko, Nagai Atsushi
First Department of Medicine, Tokyo Women's Medical University, School of Medicine, Japan.
Am J Respir Cell Mol Biol. 2002 Nov;27(5):536-41. doi: 10.1165/rcmb.4682.
The Th2 cytokines, interleukin (IL)-4 and IL-13, bind to IL-4Ralpha, and cause goblet cell metaplasia/hyperplasia with increased mucin expression in vivo. However, there is not enough evidence that these cytokines directly induce mucin production in vitro. In this study, primary epithelial cells from guinea pig trachea were cultured at an air-liquid interface, and immediately after achieving confluence at Day 7 they were treated with human recombinant IL-4 or IL-13 for 14 d. IL-13-treated cells consisted of a large number of fully mature goblet cells with a smaller number of ciliated cells. Secretory granules of the goblet cells were positive for both periodic acid-Schiff and toluidine blue, and showed exocytosis. By contrast, IL-4 failed to induce goblet cell differentiation. The electric resistances of IL-13-treated cells were lower than those of IL-4-treated cells and nontreated cells, suggesting leaky epithelia. MUC5AC protein level in cell lysates measured by ELISA was several-fold higher in IL-13-treated cells than in nontreated cells, whereas the level in IL-4-treated cells was not changed. These data suggest that human recombinant IL-13, but not IL-4, can induce differentiation into mature goblet cells that produce MUC5AC protein in guinea pig tracheal epithelial cells in vitro.
Th2细胞因子白细胞介素（IL）-4和IL-13与IL-4Rα结合，在体内可导致杯状细胞化生/增生，并伴有黏蛋白表达增加。然而，尚无足够证据表明这些细胞因子在体外能直接诱导黏蛋白产生。在本研究中，将豚鼠气管的原代上皮细胞在气液界面培养，在第7天达到汇合后立即用人重组IL-4或IL-13处理14天。经IL-13处理的细胞由大量完全成熟的杯状细胞和少量纤毛细胞组成。杯状细胞的分泌颗粒对过碘酸希夫反应和甲苯胺蓝均呈阳性，并显示出胞吐作用。相比之下，IL-4未能诱导杯状细胞分化。经IL-13处理的细胞的电阻低于经IL-4处理的细胞和未处理细胞，提示上皮细胞渗漏。通过酶联免疫吸附测定法测得的细胞裂解物中MUC5AC蛋白水平，经IL-13处理的细胞比未处理细胞高几倍，而经IL-4处理的细胞中的水平未发生变化。这些数据表明，人重组IL-13而非IL-4能在体外诱导豚鼠气管上皮细胞分化为产生MUC5AC蛋白的成熟杯状细胞。
