The roles of cathelicidin LL-37 in immune defences and novel clinical applications.
OBJECTIVE
LL-37 is the only member of the cathelicidin family of host defence peptides expressed in humans. It is primarily produced by phagocytic leucocytes and epithelial cells, and mediates a wide range of biological responses: direct killing of microorganisms, chemotaxis and chemokine induction, regulation of inflammatory responses, as well as adjuvant, angiogenic and wound healing effects. In this review we will cover the recent advances in the understanding of LL-37 biology: its activities, the mechanisms of its induction and roles in immune defence.


RESULTS
Recent studies advanced our understanding of the mechanisms controlling LL-37 expression, demonstrating the key involvement of the vitamin D3 and the hypoxia response pathways, and the impacts of commensal and pathogenic microorganisms on its production. The synergistic and antagonistic interactions between LL-37 and other immune mediators have been further elucidated. Furthermore, studies in animal models and human patients further characterized the roles of cathelicidins in immunity, with roles in infectious and inflammatory conditions. The underlying properties of LL-37 have been exploited to create innate defence regulator peptides that represent a novel immunomodulatory approach to treating infections.


CONCLUSIONS
The understanding of the biological properties and functions of LL-37 and other host defence peptides advances our knowledge of innate immunity, the interactions of the host with pathogens and the microflora, as well as the pathology of infectious and inflammatory diseases, creating many strategies and opportunities for therapeutic intervention.
Nijnik
Anastasia
A
Centre for Microbial Diseases and Immunity Research, Department of Microbiology and Immunology, 2259 Lower Mall Research Station, University of British Columbia, Vancouver, Canada.
Hancock
Robert E W
RE
D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D054804:Cathelicidins / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D015195:Drug Design; D006801:Humans; D007113:Immunity, Innate; D015533:Transcriptional Activation
D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins