Pseudomonas-Derived Ceramidase Induces Production of Inflammatory Mediators from Human Keratinocytes via Sphingosine-1-Phosphate
Figure 9
Proposed mechanism for the induction of inflammatory mediators by ceramide metabolites in human keratinocytes.
PaCDase degrades ceramide into sphingosine in the damaged stratum corneum of the skin in patients with AD. Sphingosine is subsequently converted to sphingosine-1-phosphate (S1P) by SphK. S1P binds to S1P receptor 1 and/or 3, resulting in the production and release of TNF-α. The released TNF-α binds to TNF-α receptors, and IL-8 and endothelin-1 are produced via the activation of NF-κB.