Revista de Odontologia da UNESP
https://revodontolunesp.com.br/article/doi/10.1590/1807-2577.05621
Revista de Odontologia da UNESP
Original Article

LL-37 and hBD-2 in the gingival crevicular fluid of smokers and nonsmokers with periodontitis

LL-37 e hBD-2 no fluido crevicular de fumantes e não fumantes com periodontite

Alessandra Barreto LOPES; Natália Helena COLOMBO; Naida Zanini ASSEM; Marta Aparecida Alberton NUERNBERG; Valdir Gouveia GARCIA; Cristiane DUQUE; Leticia Helena THEODORO

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Abstract

Abstract: Introduction: The association between smoking and periodontal diseases has been described in clinical and epidemiological studies.

Objective: The aim of this study was to compare the LL-37 and human β-defensin-2 (hBD-2) levels in crevicular fluid of patients with generalized periodontitis in smokers (S) and nonsmokers (NS).

Material and method: A total of 35 patients with generalized periodontitis stages III and IV, 15 NS (11 female, 4 male) and 20 S (7 female and 13 male), were included in the study. The evaluated clinical parameters were bleeding on probing (BOP), probing depth (PD) and clinical attachment level (CAL). Enzyme-linked immunosorbent assays were performed to quantify the LL-37 and hBD-2 levels in the gingival crevicular fluid of these patients. The results were analyzed statistically with the level of significance set at 5%.

Result: In relation to periodontal clinical parameters, no statistically significant difference was observed for BOP and PD between groups S and NS. There was a higher CAL in the S group than in the NS group (p = 0.0095). There was no statistically significant difference between the levels of LL-37 and hBD-2 when comparing groups S and NS (p>0.05).

Conclusion: It was concluded that smokers have a higher clinical attachment loss than nonsmokers, but that smoking did not influence the levels of LL-37 and hBD-2 in the gingival crevicular fluid in periodontitis.

Keywords

Periodontitis, antimicrobial peptides, smoking

Resumo

Resumo: Introdução: A associação entre tabagismo e doença periodontal tem sido descrito em estudos clínicos e epidemiológicos.

Objetivo: O objetivo deste estudo foi comparar os níveis de LL-37 e beta defensina-2 (hBD-2) no fluido crevicular de pacientes com periodontite generalizada fumantes (F) e não fumantes (NF).

Material e método: Um total de 35 pacientes com periodontite generalizada estágios III e IV, 15 NF (11 mulheres, 4 homens) e 20 F (7 mulheres e 13 homens), foram incluídos no estudo. Os parâmetros clínicos avaliados foram sangramento à sondagem (SS), profundidade de sondagem (PS) e nível de inserção clínica (NIC). Ensaios imuno enzimáticos foram realizados para quantificar os níveis de LL-37 e hBD-2 no fluido crevicular das gengivas dos pacientes.

Resultado: Os resultados foram analisados ​​estatisticamente, com nível de significância de 5%. Em relação aos parâmetros clínicos periodontais, não foi observada diferença estatisticamente significativa para SS e PS comparando os grupos F e NF. Houve maior NIC nos pacientes do grupo F, quando comparados ao grupo NF (p = 0,0095). Não houve diferença estatisticamente significativa entre os níveis de LL-37 e hBD-2 quando comparados os grupos F e NF (p> 0,05).

Conclusão: Concluiu-se que os fumantes apresentam maior perda de inserção clínica do que os não fumantes, mas o tabagismo não influenciou nos níveis de LL-37 e hBD-2 do fluido gengival em indivíduos com periodontite.
 

Palavras-chave

Periodontite, peptídeos antimicrobianos, fumantes

References

1 Papapanou PN, Sanz M, Buduneli N, Dietrich T, Feres M, Fine DH, et al. Periodontitis: consensus report of workgroup 2 of the 2017 World Workshop on the classification of periodontal and peri-implant diseases and conditions. J Periodontol. 2018 Jun;89(Suppl 1):S173-82. http://dx.doi.org/10.1002/JPER.17-0721. PMid:29926951.

2 van Dyke TE, Bartold PM, Reynolds EC. The nexus between periodontal inflammation and dysbiosis. Front Immunol. 2020 Mar;11:511. http://dx.doi.org/10.3389/fimmu.2020.00511. PMid:32296429.

3 Darveau RP. Periodontitis: a polymicrobial disruption of host homeostasis. Nat Rev Microbiol. 2010 Jul;8(7):481-90. http://dx.doi.org/10.1038/nrmicro2337. PMid:20514045.

4 Bergström J. Periodontitis and smoking: an evidence-based appraisal. J Evid Based Dent Pract. 2006 Mar;6(1):33-41. http://dx.doi.org/10.1016/j.jebdp.2005.12.018. PMid:17138394.

5 Johannsen A, Susin C, Gustafsson A. Smoking and inflammation: evidence for a synergistic role in chronic disease. Periodontol 2000. 2014 Feb;64(1):111-26. http://dx.doi.org/10.1111/j.1600-0757.2012.00456.x. PMid:24320959.

6 Jepsen S, Caton JG, Albandar JM, Bissada NF, Bouchard P, Cortellini P, et al. Periodontal manifestations of systemic diseases and developmental and acquired conditions: consensus report of workgroup 3 of the 2017 World Workshop on the classification of periodontal and peri-implant diseases and conditions. J Periodontol. 2018 Jun;89(Suppl 1):S237-48. http://dx.doi.org/10.1002/JPER.17-0733. PMid:29926943.

7 Bergström J. Tobacco smoking and risk for periodontal disease. J Clin Periodontol. 2003;30(2):107-13. http://dx.doi.org/10.1034/j.1600-051X.2003.00272.x. PMid:12622851.

8 Grossi SG, Genco RJ, Machtet EE, Ho AW, Koch G, Dunford R, et al. Assessment of risk for periodontal disease. II. Risk indicators for alveolar bone loss. J Periodontol. 1995;66(1):23-9. http://dx.doi.org/10.1902/jop.1995.66.1.23. PMid:7891246.

9 Gorr SU. Antimicrobial peptides of the oral cavity. Periodontol 2000. 2009;51(1):152-80. http://dx.doi.org/10.1111/j.1600-0757.2009.00310.x. PMid:19878474.

10 Makeudom A, Kulpawaropas S, Montreekachon P, Khongkhunthian S, Sastraruji T, Pothacharoen P, et al. Positive correlations between hCAP18/LL-37 and chondroitin sulphate levels in chronic periodontitis. J Clin Periodontol. 2014 Mar;41(3):252-61. http://dx.doi.org/10.1111/jcpe.12216. PMid:24372543.

11 Lu Q, Jin L, Darveau RP, Samaranayake LP. Expression of human beta-defensins-1 and -2 peptides in unresolved chronic periodontitis. J Periodontal Res. 2004 Aug;39(4):221-7. http://dx.doi.org/10.1111/j.1600-0765.2004.00727.x. PMid:15206914.

12 Dale BA, Krisanaprakornkit S. Defensin antimicrobial peptides in the oral cavity. J Oral Pathol Med. 2001 Jul;30(6):321-7. http://dx.doi.org/10.1034/j.1600-0714.2001.300601.x. PMid:11459317.

13 Duits LA, Ravensbergen B, Rademaker M, Hiemstra PS, Nibbering PH. Expression of beta-defensin 1 and 2 mRNA by human monocytes, macrophages and dendritic cells. Immunology. 2002 Aug;106(4):517-25. http://dx.doi.org/10.1046/j.1365-2567.2002.01430.x. PMid:12153515.

14 Kai-Larsen Y, Agerberth B. The role of the multifunctional peptide LL-37 in host defense. Front Biosci. 2008 May; 13:3760-7. http://dx.doi.org/10.2741/2964. PMid:18508470.

15 Cowland JB, Johnsen AH, Borregaard N. hCAP-18, a cathelin/pro-bactenecin-like protein of human neutrophil specific granules. FEBS Lett. 1995 Jul;368(1):173-6. http://dx.doi.org/10.1016/0014-5793(95)00634-L. PMid:7615076.

16 Koczulla R, von Degenfeld G, Kupatt C, Krötz F, Zahler S, Gloe T, et al. An angiogenic role for the human peptide antibiotic LL-37/hCAP-18. J Clin Invest. 2003 Jun;111(11):1665-72. http://dx.doi.org/10.1172/JCI17545. PMid:12782669.

17 Yang D, Chen Q, Schmidt AP, Anderson GM, Wang JM, Wooters J, et al. 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. 2000 Oct;192(7):1069-74. http://dx.doi.org/10.1084/jem.192.7.1069. PMid:11015447.

18 Türkoğlu O, Emingil G, Kütükçüler N, Atilla G. Gingival crevicular fluid levels of cathelicidin LL-37 and interleukin-18 in patients with chronic periodontitis. J Periodontol. 2009 Jun;80(6):969-76. http://dx.doi.org/10.1902/jop.2009.080532. PMid:19485828.

19 Dommisch H, Vorderwülbecke S, Eberhard J, Steglich M, Jepsen S. SELDI-TOF-MS of gingival crevicular fluid--a methodological approach. Arch Oral Biol. 2009 Sep;54(9):803-9. http://dx.doi.org/10.1016/j.archoralbio.2009.05.011. PMid:19555922.

20 Pütsep K, Carlsson G, Boman HG, Andersson M. Deficiency of antibacterial peptides in patients with morbus Kostmann: an observation study. Lancet. 2002 Oct;360(9340):1144-9. http://dx.doi.org/10.1016/S0140-6736(02)11201-3. PMid:12387964.

21 Matarazzo F, Figueiredo LC, Cruz SE, Faveri M, Feres M. Clinical and microbiological benefits of systemic metronidazole and amoxicillin in the treatment of smokers with chronic periodontitis: a randomized placebo-controlled study. J Clin Periodontol. 2008 Oct;35(10):885-96. http://dx.doi.org/10.1111/j.1600-051X.2008.01304.x. PMid:18727657.

22 Armitage GC. Development of a classification system for periodontal diseases and conditions. Ann Periodontol. 1999 Dec;4(1):1-6. http://dx.doi.org/10.1902/annals.1999.4.1.1. PMid:10863370.

23 Cláudio MM, Nuernberg MAA, Rodrigues JVS, Belizário LCG, Batista JA, Duque C, et al. Effects of multiple sessions of antimicrobial photodynamic therapy (aPDT) in the treatment of periodontitis in patients with uncompensated type 2 diabetes: A randomized controlled clinical study. Photodiagn Photodiagnosis Photodyn Ther. 2021 Sep;35:102451. http://dx.doi.org/10.1016/j.pdpdt.2021.102451. PMid:34303029.

24 Theodoro LH, Lopes AB, Nuernberg MAA, Cláudio MM, Miessi DMJ, Alves MLF, et al. Comparison of repeated applications of aPDT with amoxicillin and metronidazole in the treatment of chronic periodontitis: a short-term study. J Photochem Photobiol B. 2017 Sep;174:364-9. http://dx.doi.org/10.1016/j.jphotobiol.2017.08.012. PMid:28863395.

25 Radvar M, Darby I, Polster A, Arashi M, Moeintaghavi A, Sohrabi K. Pattern of cigarette smoking effect on periodontal pocketing and attachment loss: a retrospective study. Int J Dent Hyg. 2011 Nov;9(4):291-5. http://dx.doi.org/10.1111/j.1601-5037.2010.00496.x. PMid:21356029.

26 Hyman JJ, Reid BC. Epidemiologic risk factors for periodontal attachment loss among adults in the United States. J Clin Periodontol. 2003 Mar;30(3):230-7. http://dx.doi.org/10.1034/j.1600-051X.2003.00157.x. PMid:12631181.

27 Gilbert GH, Shelton BJ, Fisher MA. Forty-eight-month periodontal attachment loss incidence in a population-based cohort study: role of baseline status, incident tooth loss, and specific behavioral factors. J Periodontol. 2005 Jul;76(7):1161-70. http://dx.doi.org/10.1902/jop.2005.76.7.1161. PMid:16018760.

28 Baljoon M, Natto S, Bergström J. Long-term effect of smoking on vertical periodontal bone loss. J Clin Periodontol. 2005 Jul;32(7):789-97. http://dx.doi.org/10.1111/j.1600-051X.2005.00765.x. PMid:15966888.

29 Dietrich T, Bernimoulin JP, Glynn RJ. The effect of cigarette smoking on gingival bleeding. J Periodontol. 2004 Jan;75(1):16-22. http://dx.doi.org/10.1902/jop.2004.75.1.16. PMid:15025212.

30 Morozumi T, Kubota T, Sato T, Okuda K, Yoshie H. Smoking cessation increases gingival blood flow and gingival crevicular fluid. J Clin Periodontol. 2004 Apr;31(4):267-72. http://dx.doi.org/10.1111/j.1600-051X.2004.00476.x. PMid:15016254.

31 Gursoy UK, Könönen E. Understanding the roles of gingival beta-defensins. J Oral Microbiol. 2012;4(1):15127. http://dx.doi.org/10.3402/jom.v4i0.15127. PMid:22389759.

32 Wolgin M, Liodakis S, Pries AR, Zakrzewicz A, Kielbassa AM. HBD-1 and hBD-2 expression in HaCaT keratinocytes stimulated with nicotine. Arch Oral Biol. 2012 Jun;57(6):814-9. http://dx.doi.org/10.1016/j.archoralbio.2011.11.018. PMid:22209221.

33 Nakamura S, Saitoh M, Yamazaki M, Nishimura M, Kurashige Y, Arakawa T, et al. Nicotine induces upregulated expression of beta defensin-2 via the p38MAPK pathway in the HaCaT human keratinocyte cell line. Med Mol Morphol. 2010 Dec;43(4):204-10. http://dx.doi.org/10.1007/s00795-010-0493-4. PMid:21267696.

34 Yılmaz D, Güncü GN, Könönen E, Barış E, Çağlayan F, Gursoy UK. Overexpressions of hBD-2, hBD-3, and hCAP18/LL-37 in gingiva of diabetics with periodontitis. Immunobiology. 2015 Nov;220(11):1219-26. http://dx.doi.org/10.1016/j.imbio.2015.06.013. PMid:26092093.

35 Yong X, Chen Y, Tao R, Zeng Q, Liu Z, Jiang L, et al. Periodontopathogens and human β-defensin-2 expression in gingival crevicular fluid from patients with periodontal disease in Guangxi, China. J Periodontal Res. 2015 Jun;50(3):403-10. http://dx.doi.org/10.1111/jre.12220. PMid:25065393.

36 Pereira AL, Franco GC, Cortelli SC, Aquino DR, Costa FO, Raslan AS, et al. Influence of periodontal status and periodontopathogens on levels of oral human β-defensin-2 in saliva. J Periodontol. 2013 Oct;84(10):1445-53. http://dx.doi.org/10.1902/jop.2012.120321. PMid:23173827.

37 Brancatisano FL, Maisetta G, Barsotti F, Esin S, Miceli M, Gabriele M, et al. Reduced human beta defensin 3 in individuals with periodontal disease. J Dent Res. 2011 Feb;90(2):241-5. http://dx.doi.org/10.1177/0022034510385686. PMid:21148015.

38 Puklo M, Guentsch A, Hiemstra PS, Eick S, Potempa J. 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. 2008 Aug;23(4):328-35. http://dx.doi.org/10.1111/j.1399-302X.2008.00433.x. PMid:18582333.

39 Hosokawa I, Hosokawa Y, Komatsuzawa H, Goncalves RB, Karimbux N, Napimoga MH, et al. Innate immune peptide LL-37 displays distinct expression pattern from beta-defensins in inflamed gingival tissue. Clin Exp Immunol. 2006 Nov;146(2):218-25. http://dx.doi.org/10.1111/j.1365-2249.2006.03200.x. PMid:17034573.

40 Türkoğlu O, Eren G, Emingil G, Azarsız E, Kutukculer N, Atilla G. Does smoking affect gingival crevicular fluid LL-37 levels following non-surgical periodontal treatment in chronic periodontitis? Arch Oral Biol. 2016 Jan;61:98-105. http://dx.doi.org/10.1016/j.archoralbio.2015.10.018. PMid:26547698.

41 Davidopoulou S, Diza E, Sakellari D, Menexes G, Kalfas S. Salivary concentration of free LL-37 in edentulism, chronic periodontitis and healthy periodontium. Arch Oral Biol. 2013 Aug;58(8):930-4. http://dx.doi.org/10.1016/j.archoralbio.2013.01.003. PMid:23778112.

42 Ertugrul AS, Sahin H, Dikilitas A, Alpaslan NZ, Bozoğlan A, Tekin Y. Gingival crevicular fluid levels of human beta-defensin-2 and cathelicidin in smoker and non-smoker patients: a cross-sectional study. J Periodontal Res. 2014 Jun;49(3):282-9. http://dx.doi.org/10.1111/jre.12105. PMid:23721053.
 

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