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IL ‐33 stimulates CXCL 8/ IL ‐8 secretion in goblet cells but not normally differentiated airway cells
Author(s) -
Tanabe T.,
Shimokawaji T.,
Kanoh S.,
Rubin B. K.
Publication year - 2014
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.12283
Subject(s) - secretion , microbiology and biotechnology , goblet cell , chemistry , immunology , biology , biochemistry , epithelium , genetics
Summary Background IL ‐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. Objective We examined the effect of IL ‐33 on CXCL 8/ IL ‐8 secretion from goblet or normally differentiated human bronchial epithelial ( NHBE ) cells and signalling pathways associated with IL ‐33 activation in these cells. Methods Normal 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. Results CXCL8/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 Relevance Goblet cells secrete CXCL 8/ IL ‐8, and this is increased by IL ‐33 through ST 2R‐ ERK pathway, suggesting a mechanism for enhanced airway inflammation in the asthmatic airway with goblet cell metaplasia.