Interleukin-13 induces goblet cell differentiation in primary cell culture from Guinea pig tracheal epithelium.
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.
Kondo
Mitsuko
M
First Department of Medicine, Tokyo Women's Medical University, School of Medicine, Japan.
Tamaoki
Jun
J
Takeyama
Kiyoshi
K
Nakata
Junko
J
Nagai
Atsushi
A
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D004594:Electrophysiology; D004847:Epithelial Cells / Q000187:drug effects; D020397:Goblet Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D018793:Interleukin-13 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology; D055271:Mucin 5AC; D009077:Mucins / Q000187:drug effects / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D014132:Trachea / Q000166:cytology* / Q000187:drug effects
D018793:Interleukin-13; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D009077:Mucins; D011994:Recombinant Proteins; D015847:Interleukin-4