Epithelial cell-basophil interactions stimulate the production of IL-5 in innate allergic inflammation

Abstract

Epithelial cell-derived interleukin (IL)-33 plays an important role in the initiation and activation of innate allergic inflammation by stimulating the production of Th2 cytokines. It act as a cytokine through the transmembrane receptor ST2L, which is expressed in most of the inflammatory cells, and its activity is neutralized by the soluble spliced variant of ST2 (sST2). Basophil expresses ST2L and produces IL-5 in response to IL-33, however, the role of epithelial cell-basophil interactions in allergic inflammation is still unclear. Cultured Normal Human bronchial epithelial (NHBE) cells and human basophil cell line KU812 cells were used to study the epithelial cell-basophil interactions in the house dust mite (HDM)-induced production of IL-5. Production of IL-5, IL-33 and sST2 was evaluated by ELISA. HDM stimulated the rapid release of IL-33 from cultured NHBE cells at 1 hour after the incubation. Basophil cell line KU812 cells produced IL-5 in response to IL-33, and the conditioned medium of HDM-stimulated NHBE cells stimulated IL-5 production from KU812 cells. Co-culture of NHBE cells with KU812 cells stimulated the production of sST2 time-dependently in response to HDM, and HDM did not stimulate the production of IL-5 in co-cultured cells. These results indicate that epithelial cell-derived IL-33 stimulates the production of IL-5 from basophils, and sST2 is an important regulator of IL-33 in innate allergic inflammation.