Defensamide is an activator of sphingosine kinase (SPHK1), and significantly stimulates CAMP mRNA and protein production. Sphingosine kinase (SPHK) is a conserved lipid kinase that is essential in the production of sphingosine-1-phosphate (S1P) from the precursor sphingolipid sphingosine. Defensamide plays a potential role of in modulating innate epidermal antimicrobial defense by upregulating CAMP production[1]. Defensamide directly activated SPHK1 and increased cellular S1P content in normal cultured human keratinocytes. Treatment with defensamide (50 – 250 μM) shows a significant dose-dependent increase in CAMP mRNA expression in human keratinocytes through qRT-PCR analyses. Also, defensamide treatment significantly increased cellular S1P levels by activation of SPHK1, but not S1P lyase activity[1]. Defensamide activation of SPHK1 can stimulate innate immunity, and defensamide significantly suppressed invasion of the virulent Staphylococcus aureus into murine skin explants[1].
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