American Journal of Respiratory Cell and Molecular Biology. Vol. 27, pp. 536-541, 2002
© 2002 American Thoracic Society DOI: 10.1165/rcmb.4682
Interleukin-13 Induces Goblet Cell Differentiation in Primary Cell Culture from Guinea Pig Tracheal Epithelium
Mitsuko Kondo,
Jun Tamaoki,
Kiyoshi Takeyama,
Junko Nakata and
Atsushi Nagai
First Department of Medicine, Tokyo Women's Medical University, School of Medicine, Tokyo, Japan
Address correspondence to: Atsushi Nagai, M.D., First Department of Medicine, Tokyo Women's Medical University, School of Medicine, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. E-mail: anagai{at}chi.twmu.ac.jp
The Th2 cytokines, interleukin (IL)-4 and IL-13, bind to IL-4R , 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 airliquid interface, and immediately after achieving confluence at Day 7 they were treated with human recombinant IL-4 or IL-13 for 14 d. IL-13treated 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-13treated cells were lower than those of IL-4treated cells and nontreated cells, suggesting leaky epithelia. MUC5AC protein level in cell lysates measured by ELISA was several-fold higher in IL-13treated cells than in nontreated cells, whereas the level in IL-4treated 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.
Abbreviations: epidermal growth factor, EGF enzyme-linked immunosorbent assay, ELISA interleukin, IL ovalbumin, OVA peridoc acid-Schiff, PAS phosphate-buffered saline, PBS transmission electron microscopy, TEM
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