Effects of the cathelicidin LL-37 on intestinal epithelial barrier integrity. 
The human cathelicidin LL-37 is involved in innate immune responses, angiogenesis and wound healing.  Functions in maintenance and re-establishment of intestinal barrier integrity have not been characterized yet.  Following direct and indirect stimulation of human colonic HT-29 and Caco-2 cells with LL-37 the cellular viability, rate of apoptosis, proliferation and wound healing were determined.  Expression of mucins and growth factors was quantified by real-time PCR and Western blotting.  Direct application of LL-37 stimulated migration in Caco-2 cells expressing the proposed LL-37 receptor P2X7.  Intestinal epithelial cell (IEC) proliferation was not altered.  Indirectly, LL-37 significantly enhanced IEC migration via release of growth factors from subepithelial fibroblasts and IEC.  Furthermore, LL-37 induced the expression of protective mucins in IEC and abated tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induced apoptosis in IEC.  LL-37 induced signaling is mediated in part by the P2X7 receptor, the epidermal growth factor receptor and the p38 mitogen-activated protein kinase (MAPK).  LL-37 contributes to maintenance and re-establishment of the intestinal barrier integrity via direct and indirect pathways.  These features, in addition to its known antimicrobial properties, suggest an important role for this peptide in intestinal homeostasis.