Both sphingosine kinase 1 and 2 coordinately regulate cathelicidin antimicrobial peptide production during keratinocyte differentiation

The innate immune element, cathelicidin antimicrobial peptide (CAMP), is vital in the formation of the antimicrobial barrier in skin. CAMP production is increased during epidermal differentiation and enriched in the stratum corneum. We recently identified an endoplasmic reticulum (ER) stress-mediated sphingosine-1-phosphate (S1P)- dependent mechanism of CAMP synthesis. Interestingly, in this study, we found that S1P synthesized by an isoform of sphingosine kinase (SPHK), SPHK1, serves as a signal for CAMP synthesis; and conversely, another isoform SPHK2 likely has a suppressor role or no role in CAMP production.