Human-derived cathelicidin LL-37 directly activates mast cells to proinflammatory mediator synthesis and migratory response

Cathelicidins, a family of antimicrobial peptides, are well known for their role in host defense, particularly against bacteria. Apart from direct killing of microbes through the membrane disruption, cathelicidins can also exert immunomodulatory effects on cells involved in inflammatory processes. Considering the important role of mast cells in inflammation, the aim of this study was to determine whether LL-37, human-derived cathelicidin, can induce mast cell activation. We have observed that LL-37 directly stimulates mast cell to degranulation and production of some proinflammatory cytokines, but fails to induce cysteinyl leukotriene generation and release. We have also documented that LL-37 acts as a strong mast cell chemoattractant. In intracellular signaling in mast cells activated by LL-37 participates PLC/A(2) and, in part, MAPKs, and PI3K. In conclusion, our results indicate that cathelicidins may enhance antibacterial inflammatory response via attracting mast cell to pathogen entry site and via induction of mast cell-derived mediator release. (C) 2014 Elsevier Inc. All rights reserved.