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 Table of Contents  
REVIEW ARTICLE
Year : 2015  |  Volume : 7  |  Issue : 2  |  Page : 74-76

Role of antimicrobial peptides in periodontal innate defense mechanism


1 Department of Periodontics, Sri Sai College of Dental Surgery, Hyderabad, Telangana, India
2 Department of Pedodontics, Sri Sai College of Dental Surgery, Hyderabad, Telangana, India
3 Department of Oral Medicine and Radiology, Sri Sai College of Dental Surgery, Hyderabad, Telangana, India

Date of Web Publication22-Dec-2015

Correspondence Address:
Ashank Mishra
Department of Periodontics, Sri Sai College of Dental Surgery, Vikarabad, Hyderabad, Telangana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2249-4987.172500

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  Abstract 

The periodontal epithelium neighboring the tooth is precise to form a seal and attachment around the tooth. This exclusive function imparts unique challenges to the tissue and leads to certain vulnerabilities allied with periodontal disease, particularly in view of the continual exposure to the bacterial biofilm (dental plaque) that form that is formed on the tooth surface at the junction of the soft tissue. It is obvious that oral epithelial cells can counter unbroken microbial challenges from dental plaque by the production of antimicrobial peptides (AMPs), chemokines and cytokines that boost inflammation and immune response in periodontal tissues. AMPs are early responders of the innate immune system that search and destroy invading pathogens. The large variety of AMPs presumably allows for an effective response to the large variety of microorganisms that invade the mouth and airways. The present paper portrays the association between altered expression of AMPs and some types of periodontitis along with AMPs and their clinical significance in other oral diseases.

Keywords: Antimicrobial peptides, cathelicidins, defensins


How to cite this article:
Mishra A, Apeksha B, Koppolu P, Lingam SA. Role of antimicrobial peptides in periodontal innate defense mechanism. J Oral Res Rev 2015;7:74-6

How to cite this URL:
Mishra A, Apeksha B, Koppolu P, Lingam SA. Role of antimicrobial peptides in periodontal innate defense mechanism. J Oral Res Rev [serial online] 2015 [cited 2019 May 20];7:74-6. Available from: http://www.jorr.org/text.asp?2015/7/2/74/172500


  Introduction Top


Oral mucosa is a significant shielding interface between external and internal environments and serves as a fence to the numerous microbial species present in its moist and warm environment. The only area of the body in which hard tissues rupture through the epithelial surface is an oral cavity. The periodontal epithelium adjacent the tooth is precise to form a seal and attachment around the tooth. [1]

This exclusive function leads to certain vulnerabilities allied with periodontal disease and imparts unique challenges to the tissue, particularly in view of the incessant exposure to the bacterial biofilm (dental plaque) that form that is formed on the tooth surface at the junction of the soft tissue. Hence, this anatomical region is one where there is a substantial threat of bacterially induced inflammation and infection. Previously, the role of oral epithelium was viewed as that of a naive spectator. Nevertheless, it is now obvious that oral epithelial cells can counter unbroken microbial challenges from dental plaque by the production of chemokines, cytokines, and antimicrobial peptides (AMPs), which boost inflammation and immune response in periodontal tissues. [2]

Uncontrolled inflammation from excessive production of these pro-inflammatory molecules is considered one of the etiological factors in the pathogenesis of periodontal disease. AMPs are important contributors to maintaining the balance between health and disease in this complex environment. [3] AMPs are early responders of the innate immune system that search and destroy invading pathogens. The large variety of AMPs presumably allows for an effective reaction to the enormous diversity of microorganisms that invade the mouth and airways. In addition, a host response that involves multiple AMPs to a single pathogen is less likely to be met with antimicrobial resistance [Figure 1]. Thus, compound AMPs with dissimilar nominal inhibitory concentrations act on oral microbes. [4]
Figure 1: Illustration of role of antimicrobial peptides

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Two well-characterized families of AMPs, including cathelicidin and defensin, are existing in saliva and gingival crevicular fluid (GCF) and localized in the oral mucosa. [5]

These peptides comprise α-defensins that are expressed in the oral epithelial cells, β defensins that are secreted from and LL-37 and neutrophil granules, the lone human AMP in the cathelicidin family, which chiefly originates from neutrophil granules and to a reduced extent from oral epithelial cells. The synthesis of some of these AMPs can be significantly upregulated upon exposure to oral microorganisms; thus, these peptides are viewed as crucial effector molecules in innate immunity.


  Cathelicidins Top


Cathelicidin is a family of AMPs that comprise a cathelin domain at their N-terminus and a mature peptide at their C-terminus. The first cathelicidin AMP was sequestered from bovine neutrophils. Consequently, more than a few cathelicidin peptides were acknowledged in numerous mammals, predominantly humans. The only cathelicidin in humans, LL-37, a α-helical peptide is derived from proteolytic processing of a predecessor peptide, human cationic antimicrobial protein-18, and comprehends two leucines at its N-terminus.

Human cathelicidin is mainly isolated from neutrophil granules distinct from those that store proteolytic enzymes, such as neutrophil elastase and proteinase-3, to prevent premature activation of the cathelicidin peptide inside the neutrophils. Upon being released into neutrophil phagosomes after bacterial phagocytosis, the neutrophil cathelicidin is proteolytically cleaved into a mature LL-37 peptide by proteinase-3. [6]

In the oral cavity, LL-37 is expressed in buccal, and tongue mucosa and its expression is upregulated in the inflamed gingival tissues. Correspondingly, the concentrations of LL-37 in the gingival tissue, whether derived from neutrophils or from gingival epithelium, associate positively with the depth of the gingival crevice, signifying that LL-37 levels may be used as one diagnostic tool in inflammatory periodontal disorders. In addition, the LL-37 peptide is detected in saliva and GCF, and the LL-37 levels in GCF are significantly elevated in patients with chronic periodontitis compared with those in patients with gingivitis or those in healthy volunteers. [6]


  Defensins Top


The human defensin (HD) family can be further divided into two subfamilies, including α-defensin and β-defensin subfamilies. In the α-defensin subfamily, four of the six α-defensins, human neutrophil peptide -1, -2, -3, and -4, are synthesized and stored in neutrophil granules while the other two α-defensins, HD-5 and -6, are synthesized and stored in the granules of paneth cells, specialized epithelial cells located at the crypts of Lieberkuhn of the small intestine. [7]

In the β-defensin subfamily, four human β-defensins (hBD), hBD-1, -2, -3, and -4, are principally expressed in epithelial cells that cover some tissues and organs, predominantly skin and the mucosal surfaces of gastrointestinal, respiratory, and urogenital tracts. Nevertheless, only hBD-1, -2, and -3 are expressed in the oral cavity. HBD-1 and hBD-2 peptides are localized in differentiated epithelial cells inside the suprabasal layers of standard gingival epithelium, whereas hBD-3 peptide is expressed in undifferentiated epithelial cells within the basal layer, signifying a potential role for hBD-3 as a mediator to signal the underlying connective tissue cells. [8]


  New Antimicrobial Proteins Top


Many types of AMPs have been identified in the oral cavity, as described in the preceding sections. With the advent of saliva and GCF proteomics, it is predicted that additional AMPs will be recognized in the palate, lung, nasal epithelium clone (PLUNC) proteins, and bactericidal/permeability-increasing protein-like proteins (BPIL 1, 2, 3). The PLUNC proteins are divided into the short PLUNCs and the long PLUNCs. [4]


  Clinical Significance Top


Morbus Kostman disease is an austere congenital neutropenia that is associated with severe periodontitis. Patients with morbus Kostmann are deficient in LL-37 in neutrophils, plasma, and saliva. Patients are also scarce in alpha-defensins (30% of normal) while the plasma lactoferrin content is normal. Papillon-Lefe`vre syndrome and Haim-Munk syndrome are considered by palmoplantar keratoderma and severe periodontitis. Both diseases are caused by allelic mutations of the cathepsin C (CTSC) gene. The lysosomal enzyme CTSC is responsible for the activation of neutrophil serine proteases, which are antibacterial to Staphylococcus aureus and Aggregatibacter actinomycetemcomitans. [4]


  Conclusion Top


Substantial disparities in the expression of small cationic AMPs, including LL-37 and defensins, in periodontal tissues, GCF, and saliva, exist and may be linked with the pathogenesis of periodontal disease, as well as that of other oral inflammatory and infectious diseases. Therefore, the association midst altered expression of AMPs and some types of periodontitis should be further explored in detail. Moreover, expression of some AMPs and their clinical significance in other oral diseases should be studied further. Perhaps, some peptides could be further developed as biomarkers for diagnosis and/or prognosis of oral diseases in the future.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Dale BA, Fredericks LP. Antimicrobial peptides in the oral environment: Expression and function in health and disease. Curr Issues Mol Biol 2005;7:119-33.  Back to cited text no. 1
    
2.
McCormick TS, Weinberg A. Epithelial cell-derived antimicrobial peptides are multifunctional agents that bridge innate and adaptive immunity. Periodontol 2000 2010;54:195-206.  Back to cited text no. 2
    
3.
Suchetha A, Garg A, Lakshmi P, Bhat D, Sapna N, Apoorva SM. Adrenomedullin, periodontitis, diabetes-unraveling the equivocal relationship: A clinicobiochemical cross-sectional study. Contemp Clin Dent 2013;4:454-9.  Back to cited text no. 3
[PUBMED]  Medknow Journal  
4.
Gorr SU. Antimicrobial peptides of the oral cavity. Periodontol 2000 2009;51:152-80.  Back to cited text no. 4
    
5.
Gorr SU, Abdolhosseini M. Antimicrobial peptides and periodontal disease. J Clin Periodontol 2011;38 Suppl 11:126-41.  Back to cited text no. 5
    
6.
Krisanaprakornkit S, Khongkhunthian S. The role of antimicrobial peptides in periodontal disease (Part I): An overview of human defensins and cathelicidin. Thai J Periodont 2010;1:33-44.  Back to cited text no. 6
    
7.
Jung S, Mysliwy J, Spudy B, Lorenzen I, Reiss K, Gelhaus C, et al. Human beta-defensin 2 and beta-defensin 3 chimeric peptides reveal the structural basis of the pathogen specificity of their parent molecules. Antimicrob Agents Chemother 2011;55:954-60.  Back to cited text no. 7
    
8.
Marshall RI. Gingival defensins: Linking the innate and adaptive immune responses to dental plaque. Periodontol 2000 2004;35:14-20.  Back to cited text no. 8
    


    Figures

  [Figure 1]


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  In this article
Abstract
Introduction
Cathelicidins
Defensins
New Antimicrobia...
Clinical Signifi...
Conclusion
References
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