517 Human cathelicidin LL37 binds to scavenger receptors in inflammatory human skin diseases

Abstract

The cathelicidin antimicrobial peptide LL37 is a critical element in host defense following injury or infection, and its inappropriate expression promotes inflammatory skin diseases such as psoriasis and rosacea. We have shown that cathelicidin promotes inflammation by enabling binding of self-RNA to cell surface scavenger receptors, and that LL37 attaches to scavenger receptors in human psoriatic skin. To examine if this binding is commonly seen in other inflammatory skin diseases, we performed proximity ligation assays (PLA) using antibodies against LL37 and SR-B1, one of scavenger receptors. PLA on human skin demonstrated that the interaction between LL37 and SR-B1 was evident in situ in also rosacea, discoid lupus erythematosus, and chronic pyoderma compared to healthy skin. This result implies that the inflammatory activity of LL37 is mediated by a cell surface, scavenger receptor-dependent interaction in those inflammatory skin diseases, and that the blockade of this interaction is potentially targetable as novel anti-inflammatory therapy.