Publication: A novel role of a lipid species, sphingosine-1-phosphate, in epithelial innate immunity.
Park K, Elias PM, Shin KO, Lee YM, Hupe M, Borkowski AW, Gallo RL, Saba J, Holleran WM, Uchida Y. Mol Cell Biol. 2013 Feb;33(4):752-62. Epub 2012 Dec 10.
Synopsis and Significance: The antimicrobial peptide, LL-37, a cathelicidin, is a critical component of the skin’s innate immune defense against infectious organisms. It’s production by epidermal cells, ‘keratinocytes’, is known to be regulated by vitamin D3 through the vitamin D receptor. Here we identify a new signaling molecule, sphingosine-1-phospate. It increases production of LL-37 when the epidermis is under stress; e.g., following ultraviolet light exposure, during wound healing, or under attack by pathogenic micro-organisms. Conversely, vitamin D does not stimulate LL-37 production when the epidermis is stressed in this manner, but only under normal, baseline conditions. Identification of this new signaling mechanism will allow the development of new topical compounds, both synthetic and natural, that could be used to enhance epidermal innate immunity and antimicrobial defense, when the skin is under microbial attack from the outside.