The control of airway mucus secretion via sphingosine signals

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We cultured normal human bronchial epithelial cells in an air-liquid interface and treated with IL-13 to induce their differentiation into goblet cells. Sphingosinekinase1(SphK1) and MUC5AC expression was increased by IL-13 treatment at both protein and mRNA levels. N, N-dimethylsphingosine(DMS), a potent SphK inhibitor, decreased MUC5AC expression up-regulated by IL-13 treatment. DMS inhibited IL-13-induced ERK1/2 phosphorylation. These results suggest that SphK1 is involved in MUC5AC production induced by IL-13 upstream of ERK1/2 phosphorylation, and independent of STAT6 phosphorylation.Next we utilized the mouse asthmatic model and found that both SphK and MUC5AC expression were increased and co-localized in airway epithelium. The number of eosinophil and eosinophil peroxidase activity, levels of cytokine were improved by administration of DMS, SphK inhibitor, and FTY-720, sphingosine 1-phosphate agonist, without worsening pulmonary vascular permeability.