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Effects of the antimicrobial peptide cathelicidin (LL-37) on immortalized gingival fibroblasts infected with Porphyromonas gingivalis and irradiated with 625-nm LED light

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Abstract

Porphyromonas gingivalis causes chronic inflammatory diseases (periodontal diseases) that destroy the periodontal ligament and alveolar bone. Antimicrobial peptides are crucial components of the host defense response required to maintain cellular homeostasis during microbial invasion. Because light-emitting diode (LED) irradiation influences the host defense response against bacterial infections, we investigated its effect on immortalized gingival fibroblasts (IGFs) infected with P. gingivalis. IGFs were incubated with P. gingivalis following LED irradiation at 425, 525, and 625 nm. The dark 1 group comprised noninfected, nonirradiated IGFs, and the dark 2 group comprised nonirradiated IGFs infected with P. gingivalis. These groups served as controls. Infected cells and controls were assayed for reactive oxygen species (ROS) and were subjected to RT-PCR and Western blotting analyses to determine the levels of expression of antimicrobial peptides. LED irradiation enhanced the bactericidal effects of the antimicrobial peptide LL-37 in cells infected with P. gingivalis. Irradiation at 625 nm decreased inflammatory responses involving the release of prostaglandin E2 induced by ROS in P. gingivalis-infected IGFs. LED irradiation at 625 nm induces an anti-inflammatory response that elicits the production of antimicrobial peptides, providing an efficacious method of treatment for periodontal diseases.

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References

  1. Holt SC, Ebersole J, Felton J, Brunsvold M, Kornman KS (1988) Implantation of Bacteroides gingivalis in nonhuman primates initiates progression of periodontitis. Science 239(4835):55–57

    Article  CAS  PubMed  Google Scholar 

  2. Socransky SS, Haffajee AD (1992) The bacterial etiology of destructive periodontal disease: current concepts. J Periodontol 63(4 Suppl):322–331

    Article  CAS  PubMed  Google Scholar 

  3. Choi JI, Nakagawa T, Yamada S, Takazoe I, Okuda K (1990) Clinical, microbiological and immunological studies on recurrent periodontal disease. J Clin Periodontol 17(7 Pt 1):426–434

    CAS  PubMed  Google Scholar 

  4. Wang M, Hajishengallis G (2008) Lipid raft-dependent uptake, signalling and intracellular fate of Porphyromonas gingivalis in mouse macrophages. Cell Microbiol 10(10):2029–2042. doi:10.1111/j.1462-5822.2008.01185.x

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Liu YC, Lerner UH, Teng YT (2010) Teng YT (2010) Cytokine responses against periodontal infection: protective and destructive roles. Periodontology 2000 52(1):163–206. doi:10.1111/j.1600-0757.2009.00321.x

    Article  PubMed  Google Scholar 

  6. Zhou Q, Desta T, Fenton M, Graves DT, Amar S (2005) Cytokine profiling of macrophages exposed to Porphyromonas gingivalis, its lipopolysaccharide, or its FimA protein. Infect Immun 73(2):935–943. doi:10.1128/IAI. 73.2.935-943.2005

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Noguchi K, Yanai M, Shitashige M, Nishihara T, Ishikawa I (2000) Cyclooxygenase-2-dependent prostaglandin production by peripheral blood monocytes stimulated with lipopolysaccharides isolated from periodontopathogenic bacteria. J Periodontol 71(10):1575–1582. doi:10.1902/jop.2000.71.10.1575

    Article  CAS  PubMed  Google Scholar 

  8. Scheres N, Laine ML, de Vries TJ, Everts V, van Winkelhoff AJ (2010) Gingival and periodontal ligament fibroblasts differ in their inflammatory response to viable Porphyromonas gingivalis. J Periodontal Res 45(2):262–270. doi:10.1111/j.1600-0765.2009.01229.x

    Article  CAS  PubMed  Google Scholar 

  9. Flavell SJ, Hou TZ, Lax S, Filer AD, Salmon M, Buckley CD (2008) Fibroblasts as novel therapeutic targets in chronic inflammation. Br J Pharmacol 153:S241–S246. doi:10.1038/sj.bjp.0707487

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Dai T, Tegos GP, Zhiyentayev T, Mylonakis E, Hamblin MR (2010) Photodynamic therapy for methicillin-resistant Staphylococcus aureus infection in a mouse skin abrasion model. Lasers Surg Med 42(1):38–44. doi:10.1002/lsm.20887

    Article  PubMed Central  PubMed  Google Scholar 

  11. Walker CB (1996) The acquisition of antibiotic resistance in the periodontal microflora. Periodontology 2000(10):79–88

    Article  Google Scholar 

  12. Hancock REW, Sahl HG (2006) Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies. Nat Biotechnol 24(12):1551–1557. doi:10.1038/Nbt1267

    Article  CAS  PubMed  Google Scholar 

  13. Dale BA, Fredericks LP (2005) Antimicrobial peptides in the oral environment: expression and function in health and disease. Curr Issue Molec Biol 7(2):119–133

    CAS  Google Scholar 

  14. Nijnik A, Hancock RE (2009) The roles of cathelicidin LL-37 in immune defences and novel clinical applications. Curr Opin Hematol 16(1):41–47

    Article  CAS  PubMed  Google Scholar 

  15. Lau YE, Rozek A, Scott MG, Goosney DL, Davidson DJ, Hancock RE (2005) Interaction and cellular localization of the human host defense peptide LL-37 with lung epithelial cells. Infect Immun 73(1):583–591. doi:10.1128/IAI. 73.1.583-591.2005

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. 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 PS, Vogelmeier C, Gallo RL, Clauss M, Bals R (2003) An angiogenic role for the human peptide antibiotic LL-37/hCAP-18. J Clin Invest 111(11):1665–1672. doi:10.1172/JCI17545

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Bals R (2000) Epithelial antimicrobial peptides in host defense against infection. Respir Res 1(3):141–150. doi:10.1186/rr25

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Barber GN (2001) Host defense, viruses and apoptosis. Cell Death Differ 8(2):113–126. doi:10.1038/sj.cdd.4400823

    Article  CAS  PubMed  Google Scholar 

  19. Rosenfeld Y, Papo N, Shai Y (2006) Endotoxin (lipopolysaccharide) neutralization by innate immunity host-defense peptides. Peptide properties and plausible modes of action. J Biol Chem 281(3):1636–1643. doi:10.1074/jbc.M504327200

    Article  CAS  PubMed  Google Scholar 

  20. Nell MJ, Tjabringa GS, Vonk MJ, Hiemstra PS, Grote JJ (2004) Bacterial products increase expression of the human cathelicidin hCAP-18/LL-37 in cultured human sinus epithelial cells. FEMS Immunol Med Microbiol 42(2):225–231. doi:10.1016/j.femsim.2004.05.013

    Article  CAS  PubMed  Google Scholar 

  21. Kim S, Kim J, Lim W, Jeon S, Kim O, Koh JT, Kim CS, Choi H, Kim O (2013) In vitro bactericidal effects of 625, 525, and 425 nm wavelength (red, green, and blue) light-emitting diode irradiation. Photomed Laser Surg 31(11):554–562. doi:10.1089/pho.2012.3343

    Article  PubMed Central  PubMed  Google Scholar 

  22. Lockwood DB, Wataha JC, Lewis JB, Tseng WY, Messer RL, Hsu SD (2005) Blue light generates reactive oxygen species (ROS) differentially in tumor vs. normal epithelial cells. Dent Mater 21(7):683–688. doi:10.1016/j.dental.2004.07.022

    Article  CAS  PubMed  Google Scholar 

  23. Lim W, Lee S, Kim I, Chung M, Kim M, Lim H, Park J, Kim O, Choi H (2007) The anti-inflammatory mechanism of 635 nm light-emitting-diode irradiation compared with existing COX inhibitors. Lasers Surg Med 39(7):614–621. doi:10.1002/lsm.20533

    Article  PubMed  Google Scholar 

  24. Mongardini C, Di Tanna GL, Pilloni A (2014) Light-activated disinfection using a light-emitting diode lamp in the red spectrum: clinical and microbiological short-term findings on periodontitis patients in maintenance. A randomized controlled split-mouth clinical trial. Laser Med Sci 29(1):1–8. doi:10.1007/s10103-012-1225-x

    Article  Google Scholar 

  25. Eick S, Markauskaite G, Nietzsche S, Laugisch O, Salvi GE, Sculean A (2013) Effect of photoactivated disinfection with a light-emitting diode on bacterial species and biofilms associated with periodontitis and peri-implantitis. Photodiagn Photodyn 10(2):156–167. doi:10.1016/j.pdpdt.2012.12.001

    Article  CAS  Google Scholar 

  26. Kim J, Jung H, Lim W, Kim S, Ko Y, Karna S, Kim O, Choi Y, Choi H, Kim O (2013) Down-regulation of heat-shock protein 27-induced resistance to photodynamic therapy in oral cancer cells. J Oral Pathol Med Off Public Int Assoc Oral Pathol Am Acad Oral Pathol 42(1):9–16. doi:10.1111/j.1600-0714.2012.01155.x

    CAS  Google Scholar 

  27. Choi H, Lim W, Kim I, Kim J, Ko Y, Kwon H, Kim S, Kabir KM, Li X, Kim O, Lee Y, Kim S, Kim O (2012) Inflammatory cytokines are suppressed by light-emitting diode irradiation of P. gingivalis LPS-treated human gingival fibroblasts: inflammatory cytokine changes by LED irradiation. Lasers Med Sci 27(2):459–467. doi:10.1007/s10103-011-0971-5

    Article  PubMed  Google Scholar 

  28. Chui C, Hiratsuka K, Aoki A, Takeuchi Y, Abiko Y, Izumi Y (2012) Blue LED inhibits the growth of Porphyromonas gingivalis by suppressing the expression of genes associated with DNA replication and cell division. Lasers Surg Med 44(10):856–864. doi:10.1002/lsm.22090

    Article  PubMed  Google Scholar 

  29. Buckley CD, Pilling D, Lord JM, Akbar AN, Scheel-Toellner D, Salmon M (2001) Fibroblasts regulate the switch from acute resolving to chronic persistent inflammation. Trends Immunol 22(4):199–204

    Article  CAS  PubMed  Google Scholar 

  30. Ara T, Kurata K, Hirai K, Uchihashi T, Uematsu T, Imamura Y, Furusawa K, Kurihara S, Wang PL (2009) Human gingival fibroblasts are critical in sustaining inflammation in periodontal disease. J Periodontal Res 44(1):21–27. doi:10.1111/j.1600-0765.2007.01041.x

    Article  CAS  PubMed  Google Scholar 

  31. Vijayalakshmi M, Anand P (2012) A short review: a perspective on the role of prostaglandins (PGE2) on periodontium in health and disease. J Basic Med Allied Sci:1

  32. Noguchi K, Shitashige M, Yanai M, Morita I, Nishihara T, Murota S, Ishikawa I (1996) Prostaglandin production via induction of cyclooxygenase-2 by human gingival fibroblasts stimulated with lipopolysaccharides. Inflammation 20(5):555–568

    Article  CAS  PubMed  Google Scholar 

  33. Ryan LK, Dai JH, Yin ZW, Megjugorac N, Uhlhorn V, Yim S, Schwartz KD, Abrahams JM, Diamond G, Fitzgerald-Bocarsly P (2011) Modulation of human beta-defensin-1 (hBD-1) in plasmacytoid dendritic cells (PDC), monocytes, and epithelial cells by influenza virus, Herpes simplex virus, and Sendai virus and its possible role in innate immunity. J Leukoc Biol 90(2):343–356. doi:10.1189/Jlb.0209079

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Yang D, Chertov O, Bykovskaia SN, Chen Q, Buffo MJ, Shogan J, Anderson M, Schroder JM, Wang JM, Howard OM, Oppenheim JJ (1999) Beta-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6. Science 286(5439):525–528

    Article  CAS  PubMed  Google Scholar 

  35. Sahasrabudhe KS, Kimball JR, Morton TH, Weinberg A, Dale BA (2000) Expression of the antimicrobial peptide, human beta-defensin 1, in duct cells of minor salivary glands and detection in saliva. J Dent Res 79(9):1669–1674

    Article  CAS  PubMed  Google Scholar 

  36. Krisanaprakornkit S, Kimball JR, Weinberg A, Darveau RP, Bainbridge BW, Dale DA (2000) Inducible expression of human beta-defensin 2 by Fusobacterium nucleatum in oral epithelial cells: multiple signaling pathways and role of commensal bacteria in innate immunity and the epithelial barrier. Infect Immun 68(5):2907–2915. doi:10.1128/Iai. 68.5.2907-2915.2000

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Biragyn A, Ruffini PA, Leifer CA, Klyushnenkova E, Shakhov A, Chertov O, Shirakawa AK, Farber JM, Segal DM, Oppenheim JJ, Kwak LW (2002) Toll-like receptor 4-dependent activation of dendritic cells by beta-defensin 2. Science 298(5595):1025–1029. doi:10.1126/science.1075565

    Article  CAS  PubMed  Google Scholar 

  38. Bals R, Wang XR, Zasloff M, Wilson JM (1998) The peptide antibiotic LL-37/hCAP-18 is expressed in epithelia of the human lung where it has broad antimicrobial activity at the airway surface. Proc Natl Acad Sci U S A 95(16):9541–9546. doi:10.1073/pnas.95.16.9541

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Nizet V, Gallo RL (2003) Cathelicidins and innate defense against invasive bacterial infection. Scand J Infect Dis 35(9):670–676. doi:10.1080/00365540310015629

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korea government MSIP (2011–0030121) and MEST (NRF-2013R1A1A2061056)

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The authors have no conflict of interest.

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Correspondence to OkJoon Kim.

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JiSun Kim and SangWoo Kim contributed equally to this work.

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Kim, J., Kim, S., Lim, W. et al. Effects of the antimicrobial peptide cathelicidin (LL-37) on immortalized gingival fibroblasts infected with Porphyromonas gingivalis and irradiated with 625-nm LED light. Lasers Med Sci 30, 2049–2057 (2015). https://doi.org/10.1007/s10103-014-1698-x

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  • DOI: https://doi.org/10.1007/s10103-014-1698-x

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