Cationic antimicrobial peptide: LL-37 and its role in periodontitis
Received date: 12 Sep 2016
Accepted date: 02 Nov 2016
Published date: 17 Apr 2017
Copyright
BACKGROUND: Periodontitis i.e. inflammation of the periodontium is a multifactorial disease. Antimicrobial peptides (AMPs) which demonstrate a broad-spectrum of activity against varied number of bacteria, fungi, viruses, and parasites, and cancerous cells have been linked to periodontitis. The AMPs even possess the caliber of immunomodulation, and are significantly responsive to innate immuno-stimulation and infections. LL-37 plays a salubrious role by preventing and in treatment of chronic forms of periodontitis.
OBJECTIVE: In the present work we will review the role of antimicrobial peptide LL-37 in periodontitis.
METHODS: A systematic search was carried out from the beginning till August, 2016 using the Pubmed search engine. The keywords included “LL-37,” “periodontitis,” “Papillon–Lefevre syndrome,” “Morbus Kostmann,” “Haim-Munk syndrome” along with use of Boolean operator “and.”
RESULTS: The search resulted in identifying 67 articles which included articles linking LL-37 with periodontitis, articles on Papillon–Lefevre syndrome, Morbus Kostmann, Haim-Munk syndrome, LL-37 and periodontitis and articles on pathogenicity of periodontitis.
CONCLUSION: The literature search concluded that LL-37 plays a pivotal role in preventing and treatment of severe form of periodontitis.
Key words: LL-37; antimicrobial peptides; cathelicidin; periodontitis
Hansa Jain . Cationic antimicrobial peptide: LL-37 and its role in periodontitis[J]. Frontiers in Biology, 2017 , 12(2) : 116 -123 . DOI: 10.1007/s11515-017-1432-8
1 |
Al Aboud K, Al Aboud D (2011). Salim Haim and the syndrome that bears his name. Dermatol Online J, 17: 15
|
2 |
Aswath N, Swamikannu B, Ramakrishnan S N , Shanmugam R , Thomas J , Ramanathan A (2014). Heterozygous Ile453Val codon mutation in exon 7, homozygous single nucleotide polymorphisms in intron 2 and 5 of cathepsin C are associated with Haim-Munk syndrome. Eur J Dent, 8(1): 79–84
|
3 |
Bals R, Wang X, Zasloff M , Wilson J M (1998). The peptide antibiotic LL-37/hCAP-18 is expressed in epithelia of the human lung where it has broadantimicrobial activity at the airway surface. Proc Natl Acad Sci USA, 95(16): 9541–9546
|
4 |
Band V I, Weiss D S (2015). Mechanisms of antimicrobial peptide resistance in Gram-negative bacteria. Antibiotics (Basel), 4(1): 18–41
|
5 |
Bedran T B, Mayer M P, Spolidorio D P, Grenier D (2014). Synergistic anti-inflammatory activity of the antimicrobial peptides human beta-defensin-3 (hBD-3) and cathelicidin (LL-37) in a three-dimensional co-culture model of gingival epithelial cells and fibroblasts. PLoS One, 9(9): e106766
|
6 |
Bevec D, Cavalli F, Cavalli V , Bacher G (2008). Use of peptide ll-37 as a therapeutic agent. U.S. Patent Application 12/677,802, filed September 9
|
7 |
Carlsson G, Andersson M, Putsep K , Garwicz D , Nordenskjold M , Henter J I , Palmblad J , Fadeel B (2006). Kostmann syndrome or infantile genetic agranulocytosis, part one: celebrating 50 years of clinical and basic research on severe congenital neutropenia. Acta Paediatr, 95(12): 1526–1532
|
8 |
Chapple I L (2009). Periodontal diagnosis and treatment–where does the future lie? Periodontol 2000, 51(1): 9–24
|
9 |
Chung W O, Dommisch H, Yin L , Dale B A (2007). Expression of defensins in gingiva and their role in periodontal health and disease. Curr Pharm Des, 13(30): 3073–3083
|
10 |
Dahiya P, Kamal R, Gupta R , Bhardwaj R , Chaudhary K , Kaur S (2013). Reactive oxygen species in periodontitis. J Indian Soc Periodontol, 17(4): 411–416
|
11 |
Dale B A (2003). Periodontal epithelium: a newly recognized role in health and disease. Periodontol 2000, 30(1): 70–78
|
12 |
Dale B A, Kimball J R, Krisanaprakornkit S, Roberts F , Robinovitch M , O’Neal R , Valore E V , Ganz T, Anderson G M, Weinberg A (2001). Localized antimicrobial peptide expression in human gingiva. J Periodontal Res, 36(5): 285–294
|
13 |
Davidopoulou S, Diza E, Menexes G , Kalfas S (2012). Salivary concentration of the antimicrobial peptide LL-37 in children. Arch Oral Biol, 57(7): 865–869
|
14 |
De Yang C Q , Chen Q, Schmidt A P, Anderson G M, Wang J M, Wooters J, Oppenheim J J , Chertov O (2000). LL-37, the neutrophil granule- and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1(FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells. J Exp Med, 192(7): 1069–1074
|
15 |
Eick S, Puklo M, Adamowicz K , Kantyka T , Hiemstra P , Stennicke H , Guentsch A , Schacher B , Eickholz P , Potempa J (2014). Lack of cathelicidin processing in Papillon-Lefèvre syndrome patients reveals essential role of LL-37 inperiodontal homeostasis. Orphanet J Rare Dis, 9(1): 148
|
16 |
Frohm M, Agerberth B, Ahangari G , Stahle-Backdahl M , Liden S , Wigzell H , Gudmundsson G H (1997). The expression of the gene coding for the antibacterial peptide LL-37 is induced in human keratinocytes duringinflammatory disorders. J Biol Chem, 272(24): 15258–15263
|
17 |
Godaly G, Ambite I, Svanborg C (2015). Innate immunity and genetic determinants of urinary tract infection susceptibility. See comment in PubMed Commons below. Curr Opin Infect Dis, 28: 88–96
|
18 |
Gorr S U (2012). Antimicrobial peptides in periodontal innate defense. Front Oral Biol, 15: 84–98
|
19 |
Gorr S U, Abdolhosseini M (2011). Antimicrobial peptides and periodontal disease. J Clin Periodontol, 38(Suppl. 11): 126–141
|
20 |
Greer A, Zenobia C, Darveau R P (2013). Defensins and LL-37: a review of function in the gingival epithelium. Periodontol 2000, 63(1): 67–79
|
21 |
Gronberg A, Mahlapuu M, Stahle M , Whately-Smith C , Rollman O (2014). Treatment with LL-37 is safe and effective in enhancing healing of hard-to-heal venous leg ulcers: a randomized, placebo-controlled clinical trial. Wound Repair Regen, 22(5): 613–621
|
22 |
Gutner M, Chaushu S, Balter D , Bachrach G (2009). Saliva enables the antimicrobial activity of LL-37 in the presence of proteases of Porphyromonas gingivalis. Infect Immun, 77(12): 5558–5563
|
23 |
Guzman-Rodriguez J J , Ochoa-Zarzosa A , Lopez-Gomez R , Lopez-Meza J E (2015). Plant antimicrobial peptides as potential anticancer agents. BioMed Res Int, 735087
|
24 |
Guzman-Rodriguez J J , Ochoa-Zarzosa A , Lopez-Gomez R , Lopez-Meza J E (2015). Plant antimicrobial peptides as potential anticancer agents. BioMed Res Int, 735087
|
25 |
Hancock R E, Diamond G (2000). The role of cationic antimicrobial peptides in innate host defences. Trends Microbiol, 8(9): 402–410
|
26 |
Hatipoglu M, Saglam M, Koseoglu S , Koksal E , Keleş A , Esen H H (2015). The effectiveness of Crataegus orientalis M Bieber. (Hawthorn) extract administration in preventing alveolar bone loss in rats with experimental periodontitis. PLoS One, 10(6): e0128134
|
27 |
Henzler Wildman K A , Lee D K , Ramamoorthy A (2003). Mechanism of lipid bilayer disruption by human antimicrobial peptide, LL-37. Biochemistry, 42(21): 6545–6558
|
28 |
Inomata M, Into T, Murakami Y (2010). Suppressive effect of the antimicrobial peptide LL-37 on expression of IL-6, IL-8 and CXCL10 induced by Porphyromonas gingivalis cells and extracts in human gingival fibroblasts. Eur J Oral Sci, 118(6): 574–581
|
29 |
Into T, Inomata M, Shibata K , Murakami Y (2010). Effect of the antimicrobial peptide LL-37 on Toll-like receptors 2-, 3- and 4-triggered expression of IL-6, IL-8 andCXCL10 in human gingival fibroblasts. Cell Immunol, 264(1): 104–109
|
30 |
Jenssen H, Hamill P, Hancock R E (2006). Peptide antimicrobial agents. Clin Microbiol Rev, 19(3): 491–511
|
31 |
Khan F Y, Jan S M, Mushtaq M (2012). Papillon-Lefèvre syndrome: Case report and review of the literature. J Indian Soc Periodontol, 16(2): 261–265
|
32 |
Koczulla R, von Degenfeld G, Kupatt C , Krotz F , Zahler S , Gloe T, Issbrucker K, Unterberger P , Zaiou M , Lebherz C , Karl A, Raake P, Pfosser A , Boekstegers P , Welsch U , Hiemstra P S , Vogelmeier C , Gallo R L , Clauss M , Bals R (2003). An angiogenic role for the human peptide antibiotic LL-37/hCAP-18. J Clin Invest, 111(11): 1665–1672
|
33 |
Koziel J, Karim A Y, Przybyszewska K, Ksiazek M , Rapala-Kozik M , Nguyen K A , Potempa J (2010). Proteolytic inactivation of LL-37 by karilysin, a novel virulence mechanism of Tannerella forsythia. J Innate Immun, 2(3): 288–293
|
34 |
Leszczynska K, Namiot A, Janmey P A , Bucki R (2010). Modulation of exogenous antibiotic activity by host cathelicidin LL-37. APMIS, 118(11): 830–836
|
35 |
Leszczynska K, Namiot D, Byfield F J , Cruz K, Zendzian-Piotrowska M, Fein D E , Savage P B , Diamond S , McCulloch C A , Janmey P A , Bucki R (2013). Antibacterial activity of the human host defence peptide LL-37 and selected synthetic cationic lipids against bacteria associated with oral and upper respiratory tract infections. J Antimicrob Chemother, 68(3): 610–618
|
36 |
Lombardo Bedran T B , Palomari Spolidorio D , Grenier D (2015). Green tea polyphenol epigallocatechin-3-gallate and cranberry proanthocyanidins act in synergy withcathelicidin (LL-37) to reduce the LPS-induced inflammatory response in a three-dimensional co-culture model ofgingival epithelial cells and fibroblasts. Arch Oral Biol, 60(6): 845–853
|
37 |
Lopez-Meza J E , Ochoa-Zarzosa A , Barboza-Corona J E , Bideshi D K (2015). Antimicrobial peptides: current and potential applications in biomedical therapies. BioMed Res Int, 367243 doi:10.1155/2015/367243
|
38 |
Mahanonda R, Pichyangkul S (2007). Toll-like receptors and their role in periodontal health and disease. Periodontol 2000, 43(1): 41–55
|
39 |
Makeudom A, Kulpawaropas S, Montreekachon P , Khongkhunthian S , Sastraruji T , Pothacharoen P , Kongtawelert P , Krisanaprakornkit S (2014). Positive correlations between hCAP18/LL-37 and chondroitin sulphate levels in chronic periodontitis. J Clin Periodontol, 41(3): 252–261
|
40 |
McCrudden M T , Orr D F , Yu Y, Coulter W A, Manning G, Irwin C R , Lundy F T (2013). LL-37 in periodontal health and disease and its susceptibility to degradation by proteinases present in gingival crevicular fluid. J Clin Periodontol, 40(10): 933–941
|
41 |
Mysak J, Podzimek S, Sommerova P , Lyuya-Mi Y , Bartova J , Janatova T , Prochazkova J , Duskova J (2014). Porphyromonas gingivalis: major periodontopathic pathogen overview. J Immunol Res, 476068
|
42 |
Nakamichi Y, Horibe K, Takahashi N , Udagawa N (2014). Roles of cathelicidins in inflammation and bone loss. Odontology, 102(2): 137–146
|
43 |
Oh D Y, Koh S J (2015). Cross-regulation of innate and adaptive immunity: a new perspective for the pathogenesis of inflammatory bowel disease. Gut Liver, 9(3): 263–264
|
44 |
Oudhoff M J, Blaauboer M E, Nazmi K, Scheres N , Bolscher J G , Veerman E C (2010). The role of salivary histatin and the human cathelicidin LL-37 in wound healing and innate immunity. Biol Chem, 391(5): 541–548
|
45 |
Oyinloye B E, Adenowo A F, Kappo A P (2015). Reactive oxygen species, apoptosis, antimicrobial peptides and human inflammatory diseases. Pharmaceuticals (Basel), 8(2): 151–175
|
46 |
Oyinloye B E, Adenowo A F, Kappo A P (2015). Reactive oxygen species, apoptosis, antimicrobial peptides and human inflammatory diseases. Pharmaceuticals (Basel), 8(2): 151–175
|
47 |
Pahwa P, Lamba A K, Faraz F, Tandon S (2010). Haim-Munk syndrome. J Indian Soc Periodontol, 14(3): 201–203
|
48 |
Panteleev P V , Bolosov I A , Balandin S V , Ovchinnikova T V (2015). Structure and biological functions of β-hairpin antimicrobial Peptides. Acta Naturae, 7: 37–47
|
49 |
Peschel A, Sahl H G (2006). The co-evolution of host cationic antimicrobial peptides and microbial resistance. Nat Rev Microbiol, 4(7): 529–536
|
50 |
Puklo M, Guentsch A, Hiemstra P S , Eick S, Potempa J (2008). Analysis of neutrophil-derived antimicrobial peptides in gingival crevicular fluid suggests importance of cathelicidin LL-37 in the innate immune response against periodontogenic bacteria. Oral Microbiol Immunol, 23(4): 328–335
|
51 |
Putsep K, Carlsson G, Boman H G , Andersson M (2002). Deficiency of antibacterial peptides in patients with morbus Kostmann: an observation study. Lancet, 360(9340): 1144–1149
|
52 |
Roberts H M, Ling M R, Insall R, Kalna G , Spengler J , Grant M M , Chapple I L (2015). Impaired neutrophil directional chemotactic accuracy in chronic periodontitis patients. J Clin Periodontol, 42(1): 1–11
|
53 |
Scott M G, Davidson D J, Gold M R, Bowdish D, Hancock R E (2002). The human antimicrobial peptide LL-37 is a multifunctional modulator of innate immune responses. J Immunol, 169(7): 3883–3891
|
54 |
Shah A F, Tangade P, Agarwal S (2014). Papillon-Lefevre syndrome: Reporting consanguinity as a risk factor. Saudi Dent J, 26(3): 126–131
|
55 |
Silva N, Abusleme L, Bravo D , Dutzan N , Garcia-Sesnich J , Vernal R , Hernandez M , Gamonal J (2015). Host response mechanisms in periodontal diseases. J Appl Oral Sci, 23(3): 329–355
|
56 |
Sorensen O E, Clemmensen S N, Dahl S L, Ostergaard O, Heegaard N H , Glenthoj A , Nielsen F C , Borregaard N (2014). Papillon-Lefèvre syndrome patient reveals species-dependent requirements for neutrophil defenses. J Clin Invest, 124(10): 4539–4548
|
57 |
Takeuchi Y, Nagasawa T, Katagiri S , Kitagawara S , Kobayashi H , Koyanagi T , Izumi Y (2012). Salivary levels of antibacterial peptide (LL-37/hCAP-18) and cotinine in patients with chronic periodontitis. J Periodontol, 83(6): 766–772
|
58 |
Tao R, Jurevic R J, Coulton K K, Tsutsui M T, Roberts M C, Kimball J R, Wells N, Berndt J , Dale B A (2005). Salivary antimicrobial peptide expression and dental caries experience in children. Antimicrob Agents Chemother, 49(9): 3883–3888
|
59 |
Turkoglu O, Berdeli A, Emingil G , Atilla G (2011). A novel p.S34N mutation of CAMP gene in patients with periodontal disease. Arch Oral Biol, 56(6): 573–579
|
60 |
Turkoglu O, Emingil G, Kutukçuler N, Atilla G (2009). Gingival crevicular fluid levels of cathelicidin LL-37 and interleukin-18 in patients with chronic periodontitis. J Periodontol, 80(6): 969–976
|
61 |
Turkoglu O, Gurkan A, Emingil G , Afacan B , Toz H, Kutukçuler N, Atilla G (2015). Are antimicrobial peptides related to cyclosporine A-induced gingival overgrowth? Arch Oral Biol, 60(3): 508–515
|
62 |
Turkoglu O, Kandiloglu G, Berdeli A , Emingil G , Atilla G (2011). Antimicrobial peptide hCAP-18/LL-37 protein and mRNA expressions in different periodontal diseases. Oral Dis, 17(1): 60–67
|
63 |
Turner J, Cho Y, Dinh N N , Waring A J , Lehrer R I (1998). Activities of LL-37, a cathelin-associated antimicrobial peptide of human neutrophils. Antimicrob Agents Chemother, 42: 2206–2214
|
64 |
Usher A K, Stockley R A (2013). The link between chronic periodontitis and COPD: a common role for the neutrophil? BMC Med, 11(1): 241
|
65 |
Ximenez-Fyvie L A , Haffajee A D , Socransky S S (2000). Microbial composition of supra- and subgingival plaque in subjects with adult periodontitis. J Clin Periodontol, 27(10): 722–732
|
66 |
Yılmaz D, Guncu GN, Kononen E , Barış E , Çaglayan F , Gursoy UK (2015). Overexpressions of hBD-2, hBD-3, and hCAP18/LL-37 in gingiva of diabetics with periodontitis. Immunobiology, pii: S0171–2985: 30010–3
|
67 |
Zetterstrom R (2002). Kostmann disease-infantile genetic agranulocytosis: historical views and new aspects. Acta Paediatr, 91(12): 1279–1281
|
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