The role of antimicrobial peptides in periodontal disease

Abstract

© 2010 Nova Science Publishers, Inc. The oral cavity is a warm, moist environment, in which a number of microorganisms colonize and live in harmony as a community, a so-called biofilm. In this environment antimicrobial peptides may play a critical role in maintaining normal oral health and controlling innate and acquired immune systems in response to continuous microbial challenges in periodontal disease. Two major families of antimicrobial peptides, found in the oral cavity, are defensin and cathelicidin. Members of the defensin family are cysteine-rich peptides, synthesized by plants, insects, and mammals. These peptides vary in length and in the number of disulfide bonds, and have a beta-sheet structure. In the oral cavity, four alpha-defensins are synthesized and stored in neutrophil granules, which are converted into active peptides by proteolytic processing, while three human betadefensins (hBDs), hBD-1, hBD-2, and hBD-3, are predominantly produced by oral epithelial cells. The only member of the cathelicidin family found in humans is LL-37, an alpha-helical peptide that contains 37 amino acids and begins with two leucines at its NH3-terminus. LL-37 is derived from enzymatic cleavage of a precursor peptide, namely human cationic antimicrobial peptide-18. Clinically, differential expression of antimicrobial peptides has been reported in specific types of periodontal disease, and their presence has been shown in saliva and gingival crevicular fluid. Current evidence suggests that alpha-defensins, beta-defensins, and LL-37 have distinct, but overlapping roles in antimicrobial and pro-inflammatory activities. Several studies have shown antimicrobial activities of hBD-2, hBD-3, and LL-37 against several periodontal pathogens, suggesting their potential role as antimicrobial agents for periodontal disease. The clinical significance of antimicrobial peptides in periodontal disease has recently been demonstrated in morbus Kostmann syndrome, a severe congenital neutropenia, in which chronic periodontal infection in young patients, resulting from a deficiency of neutrophil-derived antimicrobial peptides, causes early tooth loss. Although researchers initially focused their attention on antimicrobial activities, it is now becoming evident that defensins and LL-37 are multifunctional molecules that mediate various host immune responses, and may thus represent essential molecules of innate immunity in periodontal disease. In this chapter, basic knowledge and the clinical importance of antimicrobial peptides in periodontal disease will be discussed in detail.