Skip to main content

Advertisement

SpringerLink
Log in

Photobiomodulation regulates cytokine release and new blood vessel formation during oral wound healing in rats

  • Original Article
  • Published:
Lasers in Medical Science Aims and scope Submit manuscript

Abstract

The aim of the present study was to evaluate the effects of photobiomodulation (PBM) on cytokine levels and angiogenesis during oral wound healing. Ulcers were made on the dorsum of the tongue in 48 Wistar rats. Irradiation with an indium-gallium-aluminum-phosphide (InGaAlP) laser (660 nm; output power, 40 mW; spot size, 0.04 cm2) was performed once a day on two points of the ulcer for 14 days. Two different energy densities were used: 4 J/cm2 (energy per point 0.16 J, total energy 0.32 J) and 20 J/cm2 (energy per point 0.8 J, total energy 1.6 J). Tissue levels of interleukin (IL)-1β and tumor necrosis factor (TNF)-α were investigated by enzyme-linked immunosorbent assay (ELISA). Image analysis of CD31-immunostained sections was used to investigate microvessel density (MVD). PBM increased the tissue levels of IL-1β at the early stage of oral wound healing (p < 0.01) and increased the tissue levels of TNF-α during all stages of oral wound healing (p < 0.05). PBM at a dose of 4 J/cm2 produced more significant results regarding cytokine modulation and was associated with higher MVD at day 5. Collectively, these findings indicate that cytokine modulation and increased angiogenesis are among the basic mechanisms whereby PBM improves oral wound repair.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Behm B, Babilas P, Landthaler M, Schreml S (2012) Cytokines, chemokines and growth factors in wound healing. J Eur Acad Dermatol Venereol 26(7):812–820

    Article  CAS  PubMed  Google Scholar 

  2. Barrientos S, Brem H, Stojadinovic O, Tomic-Canic M (2014) Clinical application of growth factors and cytokines in wound healing. Wound Repair Regen 22(5):569–578

    Article  PubMed  PubMed Central  Google Scholar 

  3. Olczyk P, Mencner Ł, Komosinska-Vassev K (2014) The role of the extracellular matrix components in cutaneous wound healing. Biomed Res Int 2014:747584

    PubMed  PubMed Central  Google Scholar 

  4. Ashcroft GS, Jeong MJ, Ashworth JJ, Hardman M, Jin W, Moutsopoulos N, Wild T, McCartney-Francis N, Sim D, McGrady G, Song XY, Wahl SM (2012) Tumor necrosis factor-alpha (TNF-α) is a therapeutic target for impaired cutaneous wound healing. Wound Repair Regen 20(1):38–49

    Article  PubMed  PubMed Central  Google Scholar 

  5. Kasuya A, Tokura Y (2014) Attempts to accelerate wound healing. J Dermatol Sci 76(3):169–172

    Article  PubMed  Google Scholar 

  6. Tonnesen MG, Feng X, Clark RA (2000) Angiogenesis in wound healing. J Investig Dermatol Symp Proc 5(1):40–46

    Article  CAS  PubMed  Google Scholar 

  7. Kong P, Xie X, Li F, Liu Y, Lu Y (2013) Placenta mesenchymal stem cell accelerates wound healing by enhancing angiogenesis in diabetic Goto-Kakizaki (GK) rats. Biochem Biophys Res Commun 23;438(2):410–419

    Article  Google Scholar 

  8. McLaughlin PJ, Immonen JA, Zagon IS (2013) Topical naltrexone accelerates full-thickness wound closure in type 1 diabetic rats by stimulating angiogenesis. Exp Biol Med (Maywood) 238(7):733–743

    Article  Google Scholar 

  9. Navone SE, Pascucci L, Dossena M, Ferri A, Invernici G, Acerbi F, Cristini S, Bedini G, Tosetti V, Ceserani V, Bonomi A, Pessina A, Freddi G, Alessandrino A, Ceccarelli P, Campanella R, Marfia G, Alessandri G, Parati EA (2014) Decellularized silk fibroin scaffold primed with adipose mesenchymal stromal cells improves wound healing in diabetic mice. Stem Cell Res Ther 14;5(1):7

    Article  Google Scholar 

  10. Chavan M, Jain H, Diwan N, Khedkar S, Shete A, Durkar S (2012) Recurrent aphthous stomatitis: a review. J Oral Pathol Med 41(8):577–583

    Article  PubMed  Google Scholar 

  11. Felix DH, Luker J, Scully C (2012) Oral medicine: 1. Ulcers: aphthous and other common ulcers. Dent Update 39(7):513–516, 518-9

    PubMed  Google Scholar 

  12. Leão JC, Gomes VB, Porter S (2007) Ulcerative lesions of the mouth: an update for the general medical practitioner. Clinics (Sao Paulo) 62(6):769–780

    Article  Google Scholar 

  13. Kajagar BM, Godhi AS, Pandit A, Khatri S (2012) Efficacy of low level laser therapy on wound healing in patients with chronic diabetic foot ulcers—a randomised control trial. Indian J Surg 74(5):359–363

    Article  PubMed  PubMed Central  Google Scholar 

  14. Taradaj J, Halski T, Kucharzewski M, Urbanek T, Halska U, Kucio C (2013) Effect of laser irradiation at different wavelengths (940, 808, and 658 nm) on pressure ulcer healing: results from a clinical study. Evid Based Complement Alternat Med 2013:960240

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Wagner VP, Meurer L, Martins MA, Danilevicz CK, Magnusson AS, Marques MM, Filho MS, Squarize CH, Martins MD (2013) Influence of different energy densities of laser phototherapy on oral wound healing. J Biomed Opt 18(12):128002

    Article  PubMed  PubMed Central  Google Scholar 

  16. De Souza TO, Martins MA, Bussadori SK, Fernandes KP, Tanji EY, Mesquita-Ferrari RA, Martins MD (2010) Clinical evaluation of low-level laser treatment for recurring aphthous stomatitis. Photomed Laser Surg 28(Suppl 2):S85–S88

    Google Scholar 

  17. Dillenburg CS, Martins MA, Munerato MC, Marques MM, Carrard VC, Sant’Ana Filho M, Castilho RM, Martins MD (2014) Efficacy of laser phototherapy in comparison to topical clobetasol for the treatment of oral lichen planus: a randomized controlled trial. J Biomed Opt 19(6):068002

    Article  PubMed  Google Scholar 

  18. Pellicioli AC, Martins MD, Dillenburg CS, Marques MM, Squarize CH, Castilho RM (2014) Laser phototherapy accelerates oral keratinocyte migration through the modulation of the mammalian target of rapamycin signaling pathway. J Biomed Opt 19(2):028002

    Article  PubMed  Google Scholar 

  19. Dillenburg CS, Almeida LO, Martins MD, Squarize CH, Castilho RM (2014) Laser phototherapy triggers the production of reactive oxygen species in oral epithelial cells without inducing DNA damage. J Biomed Opt 19(4):048002

    Article  PubMed  Google Scholar 

  20. Moreira MS, Velasco IT, Ferreira LS, Ariga SK, Abatepaulo F, Grinberg LT, Marques MM (2011) Effect of laser phototherapy on wound healing following cerebral ischemia by cryogenic injury. J Photochem Photobiol B 105(3):207–215

    Article  CAS  PubMed  Google Scholar 

  21. Alves AC, Vieira R, Leal-Junior E, dos Santos S, Ligeiro AP, Albertini R, Junior J, de Carvalho P (2013) Effect of low-level laser therapy on the expression of inflammatory mediators and on neutrophils and macrophages in acute joint inflammation. Arthritis Res Ther 15(5):R116

    Article  PubMed  PubMed Central  Google Scholar 

  22. dos Santos SA, Alves AC, Leal-Junior EC, Albertini R, Vieira Rde P, Ligeiro AP, Junior JA, de Carvalho Pde T (2014) Comparative analysis of two low-level laser doses on the expression of inflammatory mediators and on neutrophils and macrophages in acute joint inflammation. Lasers Med Sci 29(3):1051–1058

    PubMed  Google Scholar 

  23. Fernandes KP, Alves AN, Nunes FD, Souza NH, Silva JA Jr, Bussadori SK, Ferrari RA (2013) Effect of photobiomodulation on expression of IL-1β in skeletal muscle following acute injury. Lasers Med Sci 28(3):1043–1046

    Article  PubMed  Google Scholar 

  24. Pires D, Xavier M, Araújo T, Silva JA Jr, Aimbire F, Albertini R (2011) Low-level laser therapy (LLLT; 780 nm) acts differently on mRNA expression of anti- and pro-inflammatory mediators in an experimental model of collagenase-induced tendinitis in rat. Lasers Med Sci 26(1):85–94

    Article  PubMed  Google Scholar 

  25. Oton-Leite AF, Silva GB, Morais MO, Silva TA, Leles CR, Valadares MC, Pinezi JC, Batista AC, Mendonça EF (2015) Effect of low-level laser therapy on chemoradiotherapy-induced oral mucositis and salivary inflammatory mediators in head and neck cancer patients. Lasers Surg Med 47(4):296–305

    Article  PubMed  Google Scholar 

  26. Pereira MC, de Pinho CB, Medrado AR, Andrade Zde A, Reis SR (2010) Influence of 670 nm low-level laser therapy on mast cells and vascular response of cutaneous injuries. J Photochem Photobiol B 98(3):188–192

    Article  CAS  PubMed  Google Scholar 

  27. Feng J, Zhang Y, Xing D (2012) Low-power laser irradiation (LPLI) promotes VEGF expression and vascular endothelial cell proliferation through the activation of ERK/Sp1 pathway. Cell Signal 24(6):1116–1125

    Article  CAS  PubMed  Google Scholar 

  28. Cury V, Moretti AI, Assis L, Bossini P, Crusca Jde S, Neto CB, Fangel R, de Souza HP, Hamblin MR, Parizotto NA (2013) Low level laser therapy increases angiogenesis in a model of ischemic skin flap in rats mediated by VEGF, HIF-1α and MMP-2. J Photochem Photobiol B 125:164–170

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Colombo F, Neto Ade A, Sousa AP, Marchionni AM, Pinheiro AL, Reis SR (2013) Effect of low-level laser therapy (λ660 nm) on angiogenesis in wound healing: a immunohistochemical study in a rodent model. Braz Dent J 24(4):308–312

    Article  PubMed  Google Scholar 

  30. Antunes HS, Herchenhorn D, Small IA, Araújo CM, Viégas CM, Cabral E, Rampini MP, Rodrigues PC, Silva TG, Ferreira EM, Dias FL, Ferreira CG (2013) Phase III trial of low-level laser therapy to prevent oral mucositis in head and neck cancer patients treated with concurrent chemoradiation. Radiother Oncol 109(2):297–302

    Article  PubMed  Google Scholar 

  31. Martins MA, Martins MD, Lascala CA, Curi MM, Migliorati CA, Tenis CA, Marques MM (2012) Association of laser phototherapy with PRP improves healing of bisphosphonate-related osteonecrosis of the jaws in cancer patients: a preliminary study. Oral Oncol 48(1):79–84

    Article  PubMed  Google Scholar 

  32. Muñoz Sanchez PJ, Capote Femenías JL, Díaz Tejeda A, Tunér J (2012) The effect of 670-nm low laser therapy on herpes simplex type 1. Photomed Laser Surg 30(1):37–40

    Article  PubMed  Google Scholar 

  33. Doshi S, Jain S, Hegde R (2014) Effect of low-level laser therapy in reducing dentinal hypersensitivity and pain following periodontal flap surgery. Photomed Laser Surg 32(12):700–706

    Article  PubMed  Google Scholar 

  34. Bal MV, Keskiner İ, Sezer U, Açıkel C, Saygun I (2015) Comparison of low level laser and arginine-calcium carbonate alone or combination in the treatment of dentin hypersensitivity: a randomized split-mouth clinical study. Photomed Laser Surg 33(4):200–205

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. He WL, Yu FY, Li CJ, Pan J, Zhuang R, Duan PJ (2014) A systematic review and meta-analysis on the efficacy of low-level laser therapy in the management of complication after mandibular third molar surgery. Lasers Med Sci 30(6):1779–1788

    Article  PubMed  Google Scholar 

  36. Voronov E, Carmi Y, Apte RN (2014) The role IL-1 in tumor-mediated angiogenesis. Front Physiol 5:114

    Article  PubMed  PubMed Central  Google Scholar 

  37. Carmi Y, Voronov E, Dotan S, Lahat N, Rahat MA, Fogel M, Huszar M, White MR, Dinarello CA, Apte RN (2009) The role of macrophage-derived IL-1 in induction and maintenance of angiogenesis. J Immunol 183(7):4705–4714

    Article  CAS  PubMed  Google Scholar 

  38. Greaves NS, Ashcroft KJ, Baguneid M, Bayat A (2013) Current understanding of molecular and cellular mechanisms in fibroplasia and angiogenesis during acute wound healing. J Dermatol Sci 72(3):206–217

    Article  CAS  PubMed  Google Scholar 

  39. Corazza AV, Jorge J, Kurachi C, Bagnato VS (2007) Photobiomodulation on the angiogenesis of skin wounds in rats using different light sources. Photomed Laser Surg 25(2):102–106

    Article  PubMed  Google Scholar 

  40. Esposito E, Cuzzocrea S (2009) TNF-alpha as a therapeutic target in inflammatory diseases, ischemia-reperfusion injury and trauma. Curr Med Chem 16(24):3152–3167

    Article  CAS  PubMed  Google Scholar 

  41. Barrientos S, Stojadinovic O, Golinko MS, Brem H, Tomic-Canic M (2008) Growth factors and cytokines in wound healing. Wound Repair Regen 5:585–601

    Article  Google Scholar 

  42. Demidova-Rice TN, Salomatina EV, Yaroslavsky AN, Herman IM, Hamblin MR (2007) Low-level light stimulates excisional wound healing in mice. Lasers Surg Med 39(9):706–715

    Article  PubMed  PubMed Central  Google Scholar 

  43. Lubart R, Lavi R, Friedmann H, Rochkind S (2006) Photochemistry and photobiology of light absorption by living cells. Photomed Laser Surg 24(2):179–185

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors are grateful to Flavia Rejane Giusti for technical support.

Funding support

This study was supported by the Postgraduate Research Group, Hospital de Clínicas de Porto Alegre (GPPG/FIPE: 12-0338). Luise Meurer and Manoela Domingues Martins are research fellows funded by the Brazilian National Council for Scientific and Technological Development (CNPq).

Author information

Authors and Affiliations

  1. Department of Oral Pathology, School of Dentistry, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil

    Vivian Petersen Wagner, Marina Curra, Liana Preto Webber & Manoela Domingues Martins

  2. Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil

    Carolina Nör

  3. Gene Therapy Center, Hospital de Clínicas de Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil

    Ursula Matte

  4. Department of Pathology, Hospital de Clínicas de Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil

    Luise Meurer

Authors
  1. Vivian Petersen Wagner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marina Curra
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Liana Preto Webber
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Carolina Nör
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ursula Matte
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Luise Meurer
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Manoela Domingues Martins
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Manoela Domingues Martins.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Ethics approval

All experiments were carried out in accordance with the US National Academy of Sciences Guide for the Care and Use of Laboratory Animals and approved by the Institutional Animal Care and Use Committee of Hospital de Clínicas de Porto Alegre, Brazil, under process number 12-0338.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wagner, V.P., Curra, M., Webber, L.P. et al. Photobiomodulation regulates cytokine release and new blood vessel formation during oral wound healing in rats. Lasers Med Sci 31, 665–671 (2016). https://doi.org/10.1007/s10103-016-1904-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10103-016-1904-0

Keywords

Search

Navigation