| Summary: | LL-37 is a human cationic peptide expressed primarily by neutrophils and epithelial cells.
It is a 37 amino acid peptide that belongs to the cathelicidin family of the cationic host defense
peptides. Accumulating evidence has demonstrated that LL-37 has multiple immunomodulatory
properties. The modulatory effects of LL-37 on neutrophils were investigated here, and LL-37
was shown to be a potent inhibitor of spontaneous apoptosis in human neutrophils, signalling
through P2X₇ receptors and G-protein-coupled receptors other than the formyl peptide receptor-like-
1 molecule. Inhibition of neutrophil apoptosis involved modulation of Mcl-1 expression,
inhibition of BID and procaspase-3 cleavage, and the activation of phosphatidylinositol-3 kinase
and protein kinase C but not the extracellular signal-regulated kinase 1/2 mitogen-activated
protein kinase (ERK1/2) pathway. In addition, LL-37 modified neutrophil cytokine/chemokine
responses to pro-inflammatory stimuli in a stimulus-specific manner. Specifically, LL-37
abrogated LPS-induced TNF-a cytokine production while enhancing IL-1β elicited release of
TNF-a as well as a number of chemokines including IL-8, Gro-a, CCL-22 and Mip-la . The
increased release of chemokines induced synergistically by LL-37 and IL-1β resulted from de
novo protein synthesis and was found to be associated with the signalling through the ERK1/2
and p38 MAP kinases and nuclear factor κΒ pathways. These novel immunomodulatory
properties of LL-37 may contribute to peptide-mediated enhancement of innate host defenses
against acute infection and are of considerable significance in the development of such peptides
and their synthetic analogs as potential therapeutics for use against multiple antibiotic-resistant
infectious diseases. === Science, Faculty of === Microbiology and Immunology, Department of === Graduate
|
|---|
