Effetct of Pseudomonas aeruginosa-derived neutral ceramidase on immunological responses of three-dimensionally cultured human primary keratinocytes

点击翻译按钮获取中文摘要

A Pseudomonas aeruginosa-derived neutral ceramidase (PaCDase) isolated from a patient with atopic dermatitis was shown to effectively degrade ceramide. The ceramide metabolite sphingosine-1-phosphate (S1P) stimulated the production of inflammatory mediators such as TNF and IL-8 from three-dimensionally cultured human primary keratinocytes (3D keratinocytes). PaCDase induced the production of TNF and IL-8, and this production was dependent on ceramidase enzymatic activity. S1P enhanced the gene expression of TNF and IL-8, and this enhancement was inhibited by a sphingosine kinase inhibitor and an S1P receptor antagonist. The TNF-binding antibody infliximab suppressed the PaCDase-induced upregulation of IL-8 mRNA but not of TNF mRNA. These findings suggest that, 3D keratinocytes produce S1P from sphingosine, which is produced through the hydrolysis of ceramide by PaCDase, and then S1P induced TNF production from these cells, resulted in production of IL-8.