Study the Interrelated Triad of LL-37, Periodontal Status and Healing Outcome Following Oral Surgery

Section: Research Paper
Issue
Vol. 26 No. 2 (2026): Volume 26 Issue 2
Pages
547-558

Abstract

Abstract


Aims: This prospective clinical observation study aims to assess the correlation between saliva LL-37 levels, periodontal status, and their impact on wound healing in patients undergoing oral surgical procedures.


Materials and Methods: A total of 50 individuals were recruited: 25 patients diagnosed with chronic periodontitis (designated as group I) and 25 periodontally healthy subjects (designated as group II). Probing pocket depth (PPD), Clinical attachment loss (CAL), and bleeding on probing (BOP) were documented. Saliva LL-37 and serum C-reactive protein (CRP) concentrations were measured by ELISA. Post-operative wound recovery was evaluated using the Inflammatory Proliferative Remodeling (IPR) scale.



Results: At baseline, Group I had significantly higher levels of LL-37 (46.13±15.49) than Group II (periodontally healthy (3.61 ±2.59) (p-value = 0.000). LL-37 saliva level remained significantly higher in the periodontitis group post-operatively (p value= 0.000). Serum level of CRP followed the same trend as did LL-37, with a significant difference between the two study groups at baseline and post-operatively. Group I, delayed healing was reported, represented by the poor healing scale (IPR score =3.7±2.51) and a negative correlation with salivary LL-37 levels (r= -0.67, p < 0.01). A strong positive correlation was found (r = 0.83) between LL-37 and CRP levels at baseline and post-operatively.


Conclusion: High LL-37 levels are associated with chronic periodontal inflammatory conditions and correlate with delayed healing post-surgery. Assessing LL-37 levels may function as a potential biomarker to mirror surgical risk and design preoperative interventions in dental patients.   


 


Keywords:

Cathelicidin, LL-37, Periodontitis, Inflammation, Oral surgery. Introduction

References

  1. Kinane DF, Stathopoulou PG, Papapanou PN. Periodontal diseases. Nature reviews Disease primers. 2017 Jun 22;3(1):1-DOI: https://doi.org/10.1038/nrdp.2017.38.
  2. Nazir MA. Prevalence of periodontal disease, its association with systemic diseases and prevention. International journal of health sciences. 2017 Apr;11(2):72. PMCID: PMC5426403 PMID: 28539867.
  3. Arshad S, Awang RA, Rahman NA, Hassan A, Ahmad WM, Mohamed RN, Basha S, Karobari MI. Assessing the impact of systemic conditions on periodontal health in Malaysian population: A retrospective study. BMC Oral Health. 2024 Nov 1;24(1):1330. DOI: https://doi.org/10.1186/s12903-024-05102-y.
  4. Leite ML, Duque HM, Rodrigues GR, da Cunha NB, Franco OL. The LL-37 domain: A clue to cathelicidin immunomodulatory response?. Peptides. 2023 Jul 1;165:171011. https://doi.org/10.1016/j.peptides.2023.171011.
  5. Sun C, Zhu M, Yang Z, Pan X, Zhang Y, Wang Q, Xiao W. LL-37 secreted by epithelium promotes fibroblast collagen production: a potential mechanism of small airway remodeling in chronic obstructive pulmonary disease. Laboratory investigation. 2014 Sep 1;94(9):991-1002. https://doi.org/10.1038/labinvest.2014.86.
  6. Kzar WA, Abbas RF, Hussein HM. The Antimicrobial Peptide LL‐37 as a Predictor Biomarker for Periodontitis with the Presence and Absence of Smoking: A Case‐Control Study. BioMed Research International. 2023;2023(1):5581267. https://doi.org/10.1155/2023/5581267.
  7. Dinte E, Muntean DM, Andrei V, Boșca BA, Dudescu CM, Barbu-Tudoran L, Borodi G, Andrei S, Gal AF, Rus V, Gherman LM. In vitro and in vivo characterisation of a mucoadhesive buccal film loaded with doxycycline hyclate for topical application in periodontitis. Pharmaceutics. 2023 Feb 8;15(2):580. https://doi.org/10.3390/pharmaceutics15020580.
  8. Akiyama T, Niyonsaba F, Kiatsurayanon C, Ushio H, Fujimura T, Ueno T, Okumura K, Ogawa H, Ikeda S. The human cathelicidin LL-37 host defense peptide upregulates tight junction-related proteins and increases human epidermal keratinocyte barrier function. Journal of innate immunity. 2014 Oct 1;6(6):739-53. https://doi.org/10.1159/000362789.
  9. Yang X, Guo JL, Han J, Si RJ, Liu PP, Zhang ZR, Wang AM, Zhang J. Chitosan hydrogel encapsulated with LL-37 peptide promotes deep tissue injury healing in a mouse model. Military Medical Research. 2020 Dec;7:1-0. https://doi.org/10.1186/s40779-020-00249-5.
  10. Cheng Y, Al-Aroomi MA, Al-Worafi NA, Al Moraissi EA, Sun C. Influence of inflammation on bleeding and wound healing following surgical extraction of impacted lower third molars. BMC Oral Health. 2023 Feb 9;23(1):83. https://doi.org/10.1186/s12903-023-02754-0.
  11. Chen B, Li S, Chang Y, Zhang J, Liu J, Dong Y, Yan F. Macrophages contribute to periodontal wound healing mainly in the tissue proliferation stage. Journal of periodontal research. 2023 Feb;58(1):122-30. https://doi.org/10.1111/jre.13074.
  12. Scottish Dental Clinical Effectiveness Programme (SDCEP). Periodontal parameters. In: Prevention and Treatment of Periodontal Diseases in Primary Care. Dundee: SDCEP; 2021 [cited 2025 Apr 26]. Available from: https://www.periodontalcare.sdcep.org.uk/guidance/assessment/special-tests/full-periodontal-examination/what-should-be-recorded/periodontal-parameters/.
  13. Yahya BH, Chaushu G, Hamzani Y. Evaluation of wound healing following surgical extractions using the IPR Scale. International Dental Journal. 2021 Apr 1;71(2):133-9. https://doi.org/10.1111/idj.12622.
  14. Hashim ZA. Connotation of Serum Levels of Vitamin D3 and LL-37 with Urinary Tract Infection in Type 2 Diabetic Patients. Clinical Epidemiology and Global Health. 2026 Jan 21:102299. https://doi.org/10.1016/j.cegh.2026.102299
  15. Hosokawa I, Hosokawa Y, Komatsuzawa H, Goncalves RB, Karimbux N, Napimoga MH, Seki M, Ouhara K, Sugai M, Taubman MA, Kawai T. Innate immune peptide LL-37 displays distinct expression pattern from beta-defensins in inflamed gingival tissue. Clinical & Experimental Immunology. 2006 Nov;146(2):218-25. https://doi.org/10.1111/j.1365-2249.2006.03200.x.
  16. 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.
  17. 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 microbiology and immunology. 2008 Aug;23(4):328-35. https://doi.org/10.1111/j.1399-302X.2008.00433.xDigital Object Identifier (DOI).
  18. Svensson D, Wilk L, Mörgelin M, Herwald H, Nilsson BO. LL-37-induced host cell cytotoxicity depends on cellular expression of the globular C1q receptor (p33). Biochemical Journal. 2016 Jan 1;473(1):87-98. https://doi.org/10.1042/BJ20150798.
  19. Aarbiou J, Tjabringa GS, Verhoosel RM, Ninaber DK, White SR, Peltenburg LT, Rabe KF, Hiemstra PS. Mechanisms of cell death induced by the neutrophil antimicrobial peptides α-defensins and LL-37. Inflammation Research. 2006 Mar;55:119-27. https://doi.org/10.1007/s00011-005-0062-9.
  20. Bankell E, Dahl S, Gidlöf O, Svensson D, Nilsson BO. LL-37-induced caspase-independent apoptosis is associated with plasma membrane permeabilization in human osteoblast-like cells. Peptides. 2021 Jan 1; 135:170432. https://doi.org/10.1016/j.peptides.2020.170432.
  21. Bankell E, Liu X, Lundqvist M, Svensson D, Swärd K, Sparr E, Nilsson BO. The antimicrobial peptide LL-37 triggers release of apoptosis-inducing factor and shows direct effects on mitochondria. Biochemistry and Biophysics Reports. 2022 Mar 1;29:101192. https://doi.org/10.1016/j.bbrep.2021.101192.
  22. Chereddy KK, Her CH, Comune M, Moia C, Lopes A, Porporato PE, Vanacker J, Lam MC, Steinstraesser L, Sonveaux P, Zhu H. PLGA nanoparticles loaded with host defense peptide LL37 promote wound healing. Journal of Controlled Release. 2014 Nov 28;194:138-47. https://doi.org/10.1016/j.jconrel.2014.08.016.
  23. Ramos R, Silva JP, Rodrigues AC, Costa R, Guardão L, Schmitt F, Soares R, Vilanova M, Domingues L, Gama M. Wound healing activity of the human antimicrobial peptide LL37. Peptides. 2011 Jul 1;32(7):1469-76. https://doi.org/10.1016/j.peptides.2011.06.005.
  24. Niyonsaba F, Iwabuchi K, Someya A, Hirata M, Matsuda H, Ogawa H, Nagaoka I. A cathelicidin family of human antibacterial peptide LL‐37 induces mast cell chemotaxis. Immunology. 2002 May;106(1):20-6. https://doi.org/10.1046/j.1365-2567.2002.01398.x.
  25. Yang D, Chen Q, Schmidt AP, Anderson GM, Wang JM, Wooters J, Oppenheim JJ, Chertov O. 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. The Journal of experimental medicine. 2000 Oct 2;192(7):1069-74. https://doi.org/10.1084/jem.192.7.1069.
  26. Elssner A, Duncan M, Gavrilin M, Wewers MD. A novel P2X7 receptor activator, the human cathelicidin-derived peptide LL37, induces IL-1β processing and release. The Journal of Immunology. 2004 Apr 15;172(8):4987-94. https://doi.org/10.4049/jimmunol.172.8.4987.
  27. Kajiya M, Shiba H, Komatsuzawa H, Ouhara K, Fujita T, Takeda K, Uchida Y, Mizuno N, Kawaguchi H, Kurihara H. The antimicrobial peptide LL37 induces the migration of human pulp cells: a possible adjunct for regenerative endodontics. Journal of endodontics. 2010 Jun 1;36(6):1009-13. https://doi.org/10.1016/j.joen.2010.02.028.
  28. Tjabringa GS, Aarbiou J, Ninaber DK, Drijfhout JW, Sørensen OE, Borregaard N, Rabe KF, Hiemstra PS. The antimicrobial peptide LL-37 activates innate immunity at the airway epithelial surface by transactivation of the epidermal growth factor receptor. The Journal of Immunology. 2003 Dec 15;171(12):6690-6. https://doi.org/10.4049/jimmunol.171.12.6690.

Author

Aws Mahmood Ahmed

Department of Oral and Maxillofacial Surgery, College of Dentistry, University of Mosul, Mosul, Iraq

Identifiers

DOI: 10.33899/rpbx9504

Download this PDF file
##submission.supplementaryFiles##
pdf

Statistics

Copyright and Licensing
Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.