• T Tanabe, T Shimokawaji, S Kanoh, and B K Rubin.
• Department of Pediatrics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
• Clin. Exp. Allergy. 2014 Apr 1;44(4):540-52.

BackgroundIL-13, a helper T cell type 2 (Th2) cytokine, transforms cultured airway epithelial cells to goblet cells, and this is not inhibited by corticosteroids. IL-33 stimulates Th2 cytokines and is highly expressed in airways of persons with asthma. The effect of IL-33 on goblet cell differentiation and cytokine secretion has not been described.ObjectiveWe examined the effect of IL-33 on CXCL8/IL-8 secretion from goblet or normally differentiated human bronchial epithelial (NHBE) cells and signalling pathways associated with IL-33 activation in these cells.MethodsNormal human bronchial epithelial cells were grown to goblet or normally differentiated ciliated cell phenotype at air-liquid interface in the presence or absence of IL-13. After 14 days, differentiated cells were exposed to IL-33 for 24 h.ResultsCXCL8/IL-8 secretion into the apical (air) side of the goblet cells was greater than from normally differentiated cells (P < 0.01), and IL-33 stimulated apical CXCL8/IL-8 release from goblet cells, but not from normally differentiated cells (P < 0.01). IL-33 increased ERK 1/2 phosphorylation in goblet cells (P < 0.05), and PD98059, a MAPK/ERK kinase inhibitor, attenuated IL-33-stimulated CXCL8/IL-8 secretion from goblet cells (P < 0.001). IL-13 induced ST2 mRNA (P < 0.02) and membrane-bound ST2 protein expression on the apical side surface of goblet cells compared with normally differentiated cells, and neutralization with anti-ST2R antibody attenuated IL-33-induced apical CXCL8/IL-8 secretion from goblet cells (P < 0.02).Conclusions And Clinical RelevanceGoblet cells secrete CXCL8/IL-8, and this is increased by IL-33 through ST2R-ERK pathway, suggesting a mechanism for enhanced airway inflammation in the asthmatic airway with goblet cell metaplasia.© 2014 John Wiley & Sons Ltd.

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