Skip to main content

Advertisement

SpringerLink
Log in

Mast cell stabilization: new mechanism underlying the therapeutic effect of intense pulsed light on rosacea

  • Original Research Paper
  • Published:
Inflammation Research Aims and scope Submit manuscript

Abstract

Background

Rosacea, a chronic inflammatory disorder of the facial skin, is effectively treated by intense pulsed light (IPL).

Objective

To explore the potential molecular mechanism underlying the photobiomodulation effect of IPL for rosacea treatment.

Methods

Skin samples from patients with rosacea were subjected to histological and immunohistological staining. Ten patients were followed up after IPL treatment using the VISIA® skin analysis system, and the severity was assessed. In vivo, skin changes in mice with rosacea-like inflammation induced by intradermal injection of 320 μM LL-37 with or without IPL treatment were evaluated using L*a*b colorimetry as well as histological and immunological staining. In vitro, LL-37-stimulated mast cells (MCs) with or without IPL treatment were evaluated for protein expression of matrix metalloproteinase (MMP)-9, kallikrein-related peptidase 5 (KLK5), and cathelicidin using western blotting and qRT-PCR.

Results

Profound infiltration of inflammatory cells and evident MC degranulation were found in rosacea skin lesions. The expression of rosacea-related biomarkers and inflammatory cytokines was higher in lesional areas than in non-lesional areas, as demonstrated via immunochemical staining. In all patients, rosacea severity reduced after IPL therapy. In vivo, IPL alleviated inflammation in mice with rosacea-like inflammation, as demonstrated by the significantly decreased MMP-9, KLK5, and cathelicidin expression and reduced percentage of degranulating MCs. In vitro, IPL decreased MMP-9, KLK5, and cathelicidin expression in P815 cells, reducing the release of inflammatory cytokines and inhibiting rosacea-like inflammatory reactions.

Conclusion

The photobiomodulation effect of IPL for rosacea treatment may inhibit MC degranulation and alleviate inflammatory reactions.

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
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Data availability

All data included in this study are available upon request by contact with the corresponding author.

References

  1. Two AM, Wu W, Gallo RL, Hata TR. Rosacea. J Am Acad Dermatol. 2015;72(5):749–58. https://doi.org/10.1016/j.jaad.2014.08.028.

    Article  Google Scholar 

  2. Anzengruber F, Czernielewski J, Conrad C, Feldmeyer L, Yawalkar N, Häusermann P, Cozzio A, Mainetti C, Goldblum D, Läuchli S, Imhof L, Brand C, Laffitte E, Navarini AA. Swiss S1 guideline for the treatment of rosacea. J Eur Acad Dermatol Venereol. 2017;31(11):1775–91. https://doi.org/10.1111/jdv.14349.

    Article  CAS  Google Scholar 

  3. Gallo RL, Granstein RD, Kang S, Mannis M, Steinhoff M, Tan J, Thiboutot D. Standard classification and pathophysiology of rosacea: the 2017 update by the national rosacea society expert committee. J Am Acad Dermatol. 2018;78(1):148–55. https://doi.org/10.1016/j.jaad.2017.08.037.

    Article  Google Scholar 

  4. Gether L, Overgaard LK, Egeberg A, Thyssen JP. Incidence and prevalence of rosacea: a systematic review and meta-analysis. Br J Dermatol. 2018;179(2):282–9. https://doi.org/10.1111/bjd.16481.

    Article  CAS  Google Scholar 

  5. Yamasaki K, Di Nardo A, Bardan A, Murakami M, Ohtake T, Coda A, Dorschner RA, Bonnart C, Descargues P, Hovnanian A, Morhenn VB, Gallo RL. Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea. Nat Med. 2007;13(8):975–80. https://doi.org/10.1038/nm1616.

    Article  CAS  Google Scholar 

  6. Zhang J, Jiang P, Sheng L, Liu Y, Liu Y, Li M, Tao M, Hu L, Wang X, Yang Y, Xu Y, Liu W. A novel mechanism of carvedilol efficacy for rosacea treatment: toll-like receptor 2 inhibition in macrophages. Front Immunol. 2021;12: 609615. https://doi.org/10.3389/fimmu.2021.609615.

    Article  CAS  Google Scholar 

  7. Muto Y, Wang Z, Vanderberghe M, Two A, Gallo RL, Di Nardo A. Mast cells are key mediators of cathelicidin-initiated skin inflammation in rosacea. J Invest Dermatol. 2014;134(11):2728–36. https://doi.org/10.1038/jid.2014.222.

    Article  CAS  Google Scholar 

  8. Schwab VD, Sulk M, Seeliger S, Nowak P, Aubert J, Mess C, Rivier M, Carlavan I, Rossio P, Metze D, Buddenkotte J, Cevikbas F, Voegel JJ, Steinhoff M. Neurovascular and neuroimmune aspects in the pathophysiology of rosacea. J Investig Dermatol Symp Proc. 2011;15(1):53–62. https://doi.org/10.1038/jidsymp.2011.6.

    Article  CAS  Google Scholar 

  9. Anzengruber F, Czernielewski J, Conrad C, Feldmeyer L, Yawalkar N, Hausermann P, Cozzio A, Mainetti C, Goldblum D, Lauchli S, Imhof L, Brand C, Laffitte E, Navarini AA. Swiss S1 guideline for the treatment of rosacea. J Eur Acad Dermatol Venereol. 2017;31(11):1775–91. https://doi.org/10.1111/jdv.14349.

    Article  CAS  Google Scholar 

  10. Thiboutot D, Anderson R, Cook-Bolden F, Draelos Z, Gallo RL, Granstein RD, Kang S, Macsai M, Gold LS, Tan J. Standard management options for rosacea: the 2019 update by the national rosacea society expert committee. J Am Acad Dermatol. 2020;82(6):1501–10. https://doi.org/10.1016/j.jaad.2020.01.077.

    Article  Google Scholar 

  11. Tanghetti E, Del RJ, Thiboutot D, Gallo R, Webster G, Eichenfield LF, Stein-Gold L, Berson D, Zaenglein A. Consensus recommendations from the American acne & rosacea society on the management of rosacea, part 4: a status report on physical modalities and devices. Cutis. 2014;93(2):71–6.

    Google Scholar 

  12. Kassir R, Kolluru A, Kassir M. Intense pulsed light for the treatment of Rosacea and Telangiectasias. J Cosmet Laser Ther. 2011;13(5):216–22. https://doi.org/10.3109/14764172.2011.613480.

    Article  Google Scholar 

  13. Papageorgiou P, Clayton W, Norwood S, Chopra S, Rustin M. Treatment of rosacea with intense pulsed light: significant improvement and long-lasting results. Br J Dermatol. 2008;159(3):628–32. https://doi.org/10.1111/j.1365-2133.2008.08702.x.

    Article  CAS  Google Scholar 

  14. Zhang Y, Jiang S, Lu Y, Yan W, Yan H, Xu Y, Xu T, Li Y, Geng L, Gao X, Chen H. A decade retrospective study of light/laser devices in treating nasal rosacea. J Dermatolog Treat. 2020;31(1):84–90. https://doi.org/10.1080/09546634.2019.1580669.

    Article  CAS  Google Scholar 

  15. Hofmann MA, Lehmann P. Physical modalities for the treatment of rosacea. J Dtsch Dermatol Ges. 2016;14(Suppl 6):38–43. https://doi.org/10.1111/ddg.13144.

    Article  Google Scholar 

  16. S A, K G, K M, G H, G A, G S, G M. Rosacea management: a comprehensive review. J Cosmet Dermatol. 2022. https://doi.org/10.1111/jocd.14816.

    Article  Google Scholar 

  17. Mark KA, Sparacio RM, Voigt A, Marenus K, Sarnoff DS. Objective and quantitative improvement of rosacea-associated erythema after intense pulsed light treatment. Dermatol Surg. 2003;29(6):600–4. https://doi.org/10.1046/j.1524-4725.2003.29141.x.

    Article  Google Scholar 

  18. Serrage H, Heiskanen V, Palin WM, Cooper PR, Milward MR, Hadis M, Hamblin MR. Under the spotlight: Mechanisms of photobiomodulation concentrating on blue and green light. Photochem Photobiol Sci. 2019;18(8):1877–909. https://doi.org/10.1039/c9pp00089e.

    Article  CAS  Google Scholar 

  19. Hamblin MR. Mechanisms and applications of the anti-inflammatory effects of photobiomodulation. AIMS Biophysics. 2017;4(3):337–61. https://doi.org/10.3934/biophy.2017.3.337.

    Article  CAS  Google Scholar 

  20. Husein-Elahmed H, Steinhoff M. Light-based therapies in the management of rosacea: a systematic review with meta-analysis. Int J Dermatol. 2021. https://doi.org/10.1111/ijd.15680.

    Article  Google Scholar 

  21. Dell SJ. Intense pulsed light for evaporative dry eye disease. Clin Ophthalmol. 2017;11(20):1167–73. https://doi.org/10.2147/OPTH.S139894.

    Article  CAS  Google Scholar 

  22. Zdrada J, Stolecka-Warzecha A, Odrzywolek W, Deda A, Blonska-Fajfrowska B, Wilczynski S. Impact of IPL treatments on parameters of acne skin. J Cosmet Dermatol. 2022. https://doi.org/10.1111/jocd.14802.

    Article  Google Scholar 

  23. Fishman HA, Periman LM, Shah AA. Real-Time video microscopy of in vitro demodex death by intense pulsed light. Photobiomodul Photomed Laser Surg. 2020;38(8):472–6. https://doi.org/10.1089/photob.2019.4737.

    Article  CAS  Google Scholar 

  24. Lee JB, Bae SH, Moon KR, Na EY, Yun SJ, Lee SC. Light-emitting diodes downregulate cathelicidin, kallikrein and toll-like receptor 2 expressions in keratinocytes and rosacea-like mouse skin. Exp Dermatol. 2016;25(12):956–61. https://doi.org/10.1111/exd.13133.

    Article  CAS  Google Scholar 

  25. Taylor M, Porter R, Gonzalez M. Intense pulsed light may improve inflammatory acne through TNF-alpha down-regulation. J Cosmet Laser Ther. 2014;16(2):96–103. https://doi.org/10.3109/14764172.2013.864198.

    Article  Google Scholar 

  26. Choi HW, Abraham SN. In vitro and in vivo IgE-/antigen-mediated mast cell activation. Methods Mol Biol. 2018;1799:71–80. https://doi.org/10.1007/978-1-4939-7896-0_7.

    Article  CAS  Google Scholar 

  27. Monument MJ, Hart DA, Befus AD, Salo PT, Zhang M, Hildebrand KA. The mast cell stabilizer ketotifen fumarate lessens contracture severity and myofibroblast hyperplasia: a study of a rabbit model of posttraumatic joint contractures. J Bone Joint Surg Am. 2010;92(6):1468–77. https://doi.org/10.2106/JBJS.I.00684.

    Article  Google Scholar 

  28. Kanada KN, Nakatsuji T, Gallo RL. Doxycycline indirectly inhibits proteolytic activation of tryptic kallikrein-related peptidases and activation of cathelicidin. J Invest Dermatol. 2012;132(5):1435–42. https://doi.org/10.1038/jid.2012.14.

    Article  CAS  Google Scholar 

  29. Di Nardo A, Holmes AD, Muto Y, Huang EY, Preston N, Winkelman WJ, Gallo RL. Improved clinical outcome and biomarkers in adults with papulopustular rosacea treated with doxycycline modified-release capsules in a randomized trial. J Am Acad Dermatol. 2016;74(6):1086–92. https://doi.org/10.1016/j.jaad.2016.01.023.

    Article  CAS  Google Scholar 

  30. Choi JE, Werbel T, Wang Z, Wu CC, Yaksh TL, Di Nardo A. Botulinum toxin blocks mast cells and prevents rosacea like inflammation. J Dermatol Sci. 2019;93(1):58–64. https://doi.org/10.1016/j.jdermsci.2018.12.004.

    Article  CAS  Google Scholar 

  31. Dyson M, Luke DA. Induction of mast cell degranulation in skin by ultrasound. IEEE Trans Ultrason Ferroelectr Freq Control. 1986;33(2):194–201. https://doi.org/10.1109/t-uffc.1986.26814.

    Article  CAS  Google Scholar 

  32. Aroni K, Tsagroni E, Kavantzas N, Patsouris E, Ioannidis E. A study of the pathogenesis of rosacea: how angiogenesis and mast cells may participate in a complex multifactorial process. Arch Dermatol Res. 2008;300(3):125–31. https://doi.org/10.1007/s00403-007-0816-z.

    Article  Google Scholar 

  33. Siqueira V, Evangelista M, Dos SA, Marcos RL, Ligeiro-De-Oliveira AP, Pavani C, Damazo AS, Lino-Dos-Santos-Franco A. Light-emitting diode treatment ameliorates allergic lung inflammation in experimental model of asthma induced by ovalbumin. J Biophotonics. 2017;10(12):1683–93. https://doi.org/10.1002/jbio.201600247.

    Article  CAS  Google Scholar 

  34. Kouhkheil R, Fridoni M, Abdollhifar MA, Amini A, Bayat S, Ghoreishi SK, Chien S, Kazemi M, Bayat M. Impact of photobiomodulation and condition medium on mast cell counts, degranulation, and wound strength in infected skin wound healing of diabetic rats. Photobiomodul Photomed Laser Surg. 2019;37(11):706–14. https://doi.org/10.1089/photob.2019.4691.

    Article  Google Scholar 

Download references

Acknowledgements

Thanks for the participating investigators, patients, as well as colleagues involved in the conduct of the study. Funding for this study was provided by Chinese National Natural Science Foundation (81301384).

Funding

This work was supported by the Chinese National Natural Science Foundation (81301384).

Author information

Author notes

  1. Peiyu Jiang, Yunyi Liu and Jiawen Zhang contributed equally to this manuscript.

Authors and Affiliations

  1. Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China

    Peiyu Jiang, Yunyi Liu, Yixuan Liu, Min Li, Meng Tao, Yue Zhang & Yang Xu

  2. Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing, Jiangsu, China

    Wentao Liu

  3. Department of Dermatology, Huashan Hospital of Fudan University, Shanghai, China

    Jiawen Zhang

  4. School of Medicine and Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China

    Zongxiang Tang

Authors
  1. Peiyu Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yunyi Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jiawen Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yixuan Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Min Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Meng Tao
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yue Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Zongxiang Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Wentao Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yang Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

PYJ, JWZ and YXL: designed and supervised the study. PYJ, YYL and JWZ: completed the majority of experiment and and wrote the first draft. ML, MT, YZ and ZXT: performed material preparation, data collection and analysis. YX and WTL: reviewed and edited the first draft of the manuscript. All authors reviewed the manuscript.

Corresponding authors

Correspondence to Wentao Liu or Yang Xu.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Ethical approval

All patients provided written informed consent, and the study was approved by the Ethics Committee of the First Affiliated Hospital of Nanjing Medical University (2020-SRFA-082). Mouse care and treatment protocols were approved by Nanjing Medical University Animal Care and Use Committee (Nanjing, Jiangsu, China).

Consent to participate

Informed consent was obtained from all individual participants included in the study.

Consent for publication

The authors affirm that human research participants provided informed consent for publication of the images in (Fig. 1a–d).

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 536 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jiang, P., Liu, Y., Zhang, J. et al. Mast cell stabilization: new mechanism underlying the therapeutic effect of intense pulsed light on rosacea. Inflamm. Res. 72, 75–88 (2023). https://doi.org/10.1007/s00011-022-01635-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00011-022-01635-6

Keywords

Search

Navigation