Abstract

Cathelicidins represent a family of cationic peptides involved in host defense systems. Apart from exerting direct antimicrobial effects, cathelicidins can regulate immune response by affecting activity of cells playing role in antibacterial defense. Taking into account that mast cells are critical components of host defense the aim of this study was to determine whether rCRAMP, rat-derived cathelicidin, can influence mast cell activity. We have demonstrated that activation of fully mature rat mast cells with rCRAMP resulted in generation and release cysLTs. However, rCRAMP failed to induce mast cell degranulation and histamine release. We also found that rCRAMP stimulated rat mast cells to TNF, but not CXCL8, synthesis. What is more, this peptide induced GM-CSF, IL-1β, CCL2, and CCL3, but not IL-33 mRNA expression in mast cells. Finally, we stated that this cathelicidin serves as potent chemoattractant for rat mast cells. rCRAMP-mediated cysLT synthesis as well as mast cell migration were strongly inhibited by IL-10 pretreatment. With the use of specific inhibitors we established that activation of PLC/A2 and ERK1/2, but not p38, were required for rCRAMP-induced mast cell stimulation, while PI3K-dependent pathway is involved in both TNF synthesis and mast cell migration. Our results suggest that cathelicidins can amplify inflammatory response by causing mast cells accumulation and by stimulating these cells to release potent proinflammatory mediators.