Salivary concentration of the antimicrobial peptide LL-37 in children
Introduction
Antimicrobial peptides are essential components of innate immunity, participating in first line defence reactions at various body sites.1, 2, 3, 4 Innate immunity plays an important role in wound healing and in the maintenance of the tissue health, particularly in environments, like the oral cavity, colonized by a microbial plethora.5 Amongst the antimicrobial peptides found in the oral environment are α- and β-defensins, LL-37 antimicrobial peptide and histatins.6, 7, 8 Besides their direct bactericidal activity, these peptides have other distinct and overlapping properties, such as chemotactic activity or induction of cytokine release.9
The LL-37 antimicrobial peptide is the proteolytically processed extracellular form of human cationic antimicrobial protein of 18 kDa (hCAP-18), the only known member of cathelicidins in humans,10 found in the secondary granules of neutrophils and various other cells.11 LL-37 is present in the pulmonary12, 13 and the digestive system14 and it has also been detected in plasma,15, 16 sweat,17 skin,18, 19 and human milk.20 Regarding the oral cavity, LL-37 has been detected in saliva,21 whilst the peptide itself or its mRNA or both have been detected in salivary glands,21, 22 in lingual epithelium and palatal mucosa.23 Following inflammatory stimulation, LL-37 is released at the inflamed sites mainly by neutrophils that migrate through the junctional epithelium.24, 25 This pattern of expression implies a possible protective role of the peptide on both hard and soft oral tissues.6
The aetiology of periodontal diseases and dental caries is the microbial plaque accumulated on dental surfaces.26, 27, 28 Controlling microbial dental plaque is of primary importance in preventing and treating these diseases. LL-37 has a broad antimicrobial activity against both cariogenic and periopathogenic bacteria29, 30, 31, 32 and its role in maintaining oral health has recently been suggested.6 Inheritable neutrophil defects leading to a lack of LL-37 have been associated to severe periodontitis,33, 34 whilst low salivary levels of LL-37 were frequently detected in caries susceptible subjects.35 Recently, further studies give new insight in the role of the LL-37 antimicrobial peptide in periodontal disease.36, 37, 38
Limited information exists on the salivary antimicrobial peptide concentration in adults and children.35, 39 Moreover, the concentration of LL-37 was determined by semi-quantitative methods in the study dealing with children.35 Thus, we aimed to examine the LL-37 concentration in saliva of children and its possible correlation to age, gender, type of dentition and caries experience using a quantitative method.
Section snippets
Study design
The study was approved by the Ethics Committee of the Dental School in Aristotle University of Thessaloniki. The purpose and procedures were fully explained and informed consents, in accordance with Helsinki Declaration, were signed by the parents or guardians of the children before enrolled in the study.
The study group consisted of 49 children, 21 boys and 28 girls, 2–18 years old (mean age 8.7 years). All children were examined by trained pedodontists using standardized clinical procedures.
Results
Out of 49 children, 30 were caries free (DT score 0), 9 had low to moderate caries activity (DT score 1–3) and 10 exhibited high caries activity (DT score ≥4). The data is presented in Table 1.
The LL-37 antimicrobial peptide was detected in all saliva samples. Its concentration considerably varied from 0.22 to 275 ng/ml in the samples. The median value was 22 ng/ml. Younger children mostly had low LL-37 concentration (Fig. 1) and a positive significant correlation was observed between peptide
Discussion
It becomes evident from the present results that LL-37 antimicrobial peptide is secreted in the saliva already at early childhood. At this age, the concentration of the peptide is generally low but it increases with the age showing a tendency to reach a plateau at late adolescence. The concentration of the peptide widely varies not only with the age but also with the gender and the subject, showing up to 100-fold differences amongst adolescents. Being at the level of ng/ml, the salivary
Funding
There is no conflict of interest of any of the authors.
Competing interests
There is no financial support other than from Aristotle University of Thessaloniki.
Ethical approval
The study was approved by the Ethics Committee of the Dental School in Aristotle University of Thessaloniki. The purpose and procedures were fully explained and informed consents, in accordance with Helsinki Declaration, were signed by the parents or guardians of the children before enrolled in the study. Reference Number 127/27-11-08.
References (51)
- et al.
Skin peptides: biological activity and therapeutic opportunities
J Pharm Sci
(2008) Innate immunity, antimicrobial peptides, and protection of the oral cavity
Lancet
(2002)- et al.
LL-37, the only human member of the cathelicidin family of antimicrobial peptides
Biochim Biophys Acta
(2006) - et al.
Beta-defensins and LL-37 in bronchoalveolar lavage fluid of patients with cystic fibrosis
J Cyst Fibros
(2004) - et al.
Multiple trauma induces serum production of host defence peptides
Injury
(2012) - et al.
Cathelicidin anti-microbial peptide expression in sweat, an innate defense system for the skin
J Invest Dermatol
(2002) - et al.
Protective roles of the skin against infection: implication of naturally occurring human antimicrobial agents beta-defensins, cathelicidin LL-37 and lysozyme
J Dermatol Sci
(2005) - et al.
Antimicrobial peptides and the skin immune defense system
J Allergy Clin Immunol
(2008) - et al.
Deficiency of antibacterial peptides in patients with morbus Kostmann: an observation study
Lancet
(2002) - et al.
Determinants of salivary alpha-amylase in humans and methodological considerations
Psychoneuroendocrinology
(2009)
A novel p.S34N mutation of CAMP gene in patients with periodontal disease
Arch Oral Biol
Age and gender related differences in human parotid gland gene expression
Arch Oral Biol
Expression of secretory proteins in oral fluid after orthodontic tooth movement
Am J Orthod Dentofacial Orthop
Defensins: antimicrobial peptides of innate immunity
Nat Rev Immunol
Human defensins and LL-37 in mucosal immunity
J Leukoc Biol
Host defense peptides in the oral cavity and the lung: similarities and differences
J Dent Res
Antimicrobial peptides in the oral environment: expression and function in health and disease
Curr Issues Mol Biol
Expression of defensins in gingiva and their role in periodontal health and disease
Curr Pharm Des
Antimicrobial peptides in saliva and salivary glands: their roles in the oral defense system
Oral Med Pathol
Immunomodulatory activities of small host defense peptides
Antimicrob Agents Chemother
Human cathelicidin, hCAP-18, is processed to the antimicrobial peptide LL-37 by extracellular cleavage with proteinase 3
Blood
LL-37 complexation with glycosaminoglycans in cystic fibrosis lungs inhibits antimicrobial activity, which can be restored by hypertonic saline
J Immunol
Antimicrobial peptides are present in immune and host defense cells of the human respiratory and gastrointestinal tracts
Cell Tissue Res
Maternal plasma level of antimicrobial peptide LL37 is a major determinant factor of neonatal plasma LL37 level
Acta Paediatr
Expression and secretion of cathelicidin antimicrobial peptides in murine mammary glands and human milk
Pediatr Res
Cited by (58)
Antimicrobial peptides for the prevention and treatment of dental caries: A concise review
2021, Archives of Oral BiologyCitation Excerpt :This review indicated that several natural antimicrobial peptides play a role in the host’s defence system against cariogenic pathogens. However, the mechanism is still unclear and requires more studies to gain support (Davidopoulou et al., 2012). This review also summarised three methods for developing novel antimicrobial peptides for the management of dental caries.
Dental caries in children and vitamin D deficiency: a narrative review
2024, European Journal of Pediatrics