Polynucleotides Enhance Skin Barrier Function and Reduce Inflammation in a 2,4-Dinitrochlorobenzene-Induced Mouse Model of Atopic Dermatitis
Ye Jin Ha
Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
Search for more papers by this authorKa Hee Tak
Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
Search for more papers by this authorJong Lyul Lee
Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
Division of Colon and Rectal Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
Search for more papers by this authorChan Wook Kim
Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
Division of Colon and Rectal Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
Search for more papers by this authorIk Jun Moon
Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
Search for more papers by this authorCorresponding Author
Yong Sik Yoon
Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
Division of Colon and Rectal Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
Search for more papers by this authorYe Jin Ha
Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
Search for more papers by this authorKa Hee Tak
Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
Search for more papers by this authorJong Lyul Lee
Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
Division of Colon and Rectal Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
Search for more papers by this authorChan Wook Kim
Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
Division of Colon and Rectal Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
Search for more papers by this authorIk Jun Moon
Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
Search for more papers by this authorCorresponding Author
Yong Sik Yoon
Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
Division of Colon and Rectal Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
Search for more papers by this authorABSTRACT
Background
Atopic dermatitis (AD) is a chronic inflammatory dermatological disorder characterized by skin barrier dysfunction, dry skin, pruritus, and aberrant immune responses to external stimuli. Although polynucleotides (PNs) have anti-inflammatory properties, their effect on AD remains unexplored.
Materials and Methods
This study investigated the effects of PNs on a 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse model. The effects were evaluated by the dermatitis severity score (DSS), the spleen index, the serum immunoglobulin E (IgE) concentration, trans-epidermal water loss (TEWL), histological findings, and the expression levels of cytokine mRNA and filaggrin protein in skin tissue.
Results
Topical application of PNs significantly reduced the DSS, the spleen index, the serum IgE concentration, and TEWL compared with the control. Additionally, histopathological analysis showed that PNs reduced epidermal and dermal thickness, the mast cell count, collagen deposition, and eosinophil infiltration in the dermis. Moreover, PNs significantly downregulated the expression of key inflammatory cytokines, including interleukin (IL)-4, IL-5, IL-13, IL-25, IL-33, and thymic stromal lymphopoietin (TSLP), in affected skin tissue. Immunohistochemical (IHC) staining and Western blot revealed that PNs inhibited DNCB-induced suppression of filaggrin. A combination of hyaluronic acid (HA) and PNs showed enhanced efficacy compared with PNs alone, particularly for reducing the serum IgE concentration and TEWL and increasing filaggrin expression.
Conclusion
These results suggest that PNs are potential candidates to treat AD because they possess anti-inflammatory properties and improve skin barrier function.
Conflicts of Interest
The authors declare no conflicts of interest.
Open Research
Data Availability Statement
No data are availible for this study as no datasets were generated or analyzed during the current research.
References
- 1T. Bieber, “Atopic Dermatitis: An Expanding Therapeutic Pipeline for a Complex Disease,” Nature Reviews Drug Discovery 21, no. 1 (2022): 21–40.
- 2S. Weidinger and N. Novak, “Atopic Dermatitis,” Lancet 387, no. 10023 (2016): 1109–1122.
- 3T. Czarnowicki, J. G. Krueger, and E. Guttman-Yassky, “Skin Barrier and Immune Dysregulation in Atopic Dermatitis: An Evolving Story With Important Clinical Implications,” Journal of Allergy and Clinical Immunology: In Practice 2, no. 4 (2014): 371–379. quiz 380-371.
- 4G. Yang, J. K. Seok, H. C. Kang, Y. Y. Cho, H. S. Lee, and J. Y. Lee, “Skin Barrier Abnormalities and Immune Dysfunction in Atopic Dermatitis,” International Journal of Molecular Sciences 21, no. 8 (2020): 2867.
- 5Q. Wu, X. Mo, Y. Lin, et al., “Inhibitory Effects of Isoliquiritin on an Atopic Dermatitis Model Through the CD177/JAK2/STAT Pathway In Vitro and In Vivo,” Annals of Translational Medicine 10, no. 18 (2022): 980.
- 6M. Cavallini, E. Bartoletti, L. Maioli, et al., “Consensus Report on the Use of PN-HPT™ (Polynucleotides Highly Purified Technology) in Aesthetic Medicine,” Journal of Cosmetic Dermatology 20, no. 3 (2021): 922–928.
- 7S. M. Shin, E. J. Baek, K. H. Kim, K. J. Kim, and E. J. Park, “Polydeoxyribonucleotide Exerts Opposing Effects on ERK Activity in Human Skin Keratinocytes and Fibroblasts,” Molecular Medicine Reports 28, no. 2 (2023): 148.
- 8G. Picciolo, F. Mannino, N. Irrera, et al., “PDRN, a Natural Bioactive Compound, Blunts Inflammation and Positively Reprograms Healing Genes in an “In Vitro” Model of Oral Mucositis,” Biomedicine & Pharmacotherapy 138 (2021): 111538.
- 9S. Jo, A. Baek, Y. Cho, et al., “Therapeutic Effects of Polydeoxyribonucleotide in an In Vitro Neuronal Model of Ischemia/Reperfusion Injury,” Scientific Reports 13, no. 1 (2023): 6004.
- 10R. C. Gupta, R. Lall, A. Srivastava, and A. Sinha, “Hyaluronic Acid: Molecular Mechanisms and Therapeutic Trajectory,” Frontiers in Veterinary Science 6 (2019): 192.
- 11V. Voinchet, P. Vasseur, and J. Kern, “Efficacy and Safety of Hyaluronic Acid in the Management of Acute Wounds,” American Journal of Clinical Dermatology 7, no. 6 (2006): 353–357.
- 12H. Roehrs, J. G. Stocco, F. Pott, G. Blanc, M. J. Meier, and F. A. Dias, “Dressings and Topical Agents Containing Hyaluronic Acid for Chronic Wound Healing,” Cochrane Database of Systematic Reviews (Online) 7, no. 7 (2023): Cd012215.
- 13M. N. Leite and M. A. C. Frade, “Efficacy of 0.2% Hyaluronic Acid in the Healing of Skin Abrasions in Rats,” Heliyon 7, no. 7 (2021): e07572.
- 14B. W. Zheng, B. Y. Wang, W. L. Xiao, Y. J. Sun, C. Yang, and B. T. Zhao, “Different Molecular Weight Hyaluronic Acid Alleviates Inflammation Response in DNFB-Induced Mice Atopic Dermatitis and LPS-Induced RAW 264.7 Cells,” Life Sciences 301 (2022): 120591.
- 15D. Dallari, G. Sabbioni, N. Del Piccolo, et al., “Efficacy of Intra-Articular Polynucleotides Associated With Hyaluronic Acid Versus Hyaluronic Acid Alone in the Treatment of Knee Osteoarthritis: A Randomized, Double-Blind, Controlled Clinical Trial,” Clinical Journal of Sport Medicine 30, no. 1 (2020): 1–7.
- 16G. De Caridi, M. Massara, I. Acri, et al., “Trophic Effects of Polynucleotides and Hyaluronic Acid in the Healing of Venous Ulcers of the Lower Limbs: A Clinical Study,” International Wound Journal 13, no. 5 (2016): 754–758.
- 17J. H. Kim, T. R. Kwon, S. E. Lee, et al., “Comparative Evaluation of the Effectiveness of Novel Hyaluronic Acid-Polynucleotide Complex Dermal Filler,” Scientific Reports 10, no. 1 (2020): 5127.
- 18Y. J. Ha, K. H. Tak, J. M. Jung, et al., “The Effect of Polynucleotide-Hyaluronic Acid Hydrogel in the Recovery After Mechanical Skin Barrier Disruption,” Skin Research and Technology: Official Journal of International Society for Bioengineering and the Skin (Isbs) [And] International Society for Digital Imaging of Skin (Isdis) [And] International Society for Skin Imaging (Issi) 30, no. 9 (2024): e70068.
- 19T. Zhang, J. Qiu, X. Wu, S. Huang, H. Yuan, and S. Park, “Schizonepeta Tenuifolia With Alpinia Oxyphylla Alleviates Atopic Dermatitis and Improves the Gut Microbiome in Nc/Nga Mice,” Pharmaceutics 12, no. 8 (2020): 722.
- 20S. H. Yan, Y. Chen, Z. Q. Huang, et al., “Acupoint Autohemotherapy Attenuates DNCB-Induced Atopic Dermatitis and Activates Regulatory T Cells in BALB/c Mice,” Journal of Inflammation Research 17 (2024): 2839–2850.
- 21J. Bajgai, A. Fadriquela, J. Ara, et al., “Balneotherapeutic Effects of High Mineral Spring Water on the Atopic Dermatitis-Like Inflammation in Hairless Mice via Immunomodulation and Redox Balance,” BMC Complementary and Alternative Medicine [Electronic Resource] 17, no. 1 (2017): 481.
- 22Z. Wang, H. Zhang, C. Qi, et al., “Ursolic Acid Ameliorates DNCB-Induced Atopic Dermatitis-Like Symptoms in Mice by Regulating TLR4/NF-κB and Nrf2/HO-1 Signaling Pathways,” International Immunopharmacology 118 (2023): 110079.
- 23Y. Aono, Y. Suzuki, R. Horiguchi, et al., “CD109 on Dendritic Cells Regulates Airway Hyperreactivity and Eosinophilic Airway Inflammation,” American Journal of Respiratory Cell and Molecular Biology 68, no. 2 (2023): 201–212.
- 24A. Gilhar, K. Reich, A. Keren, K. Kabashima, M. Steinhoff, and R. Paus, “Mouse Models of Atopic Dermatitis: A Critical Reappraisal,” Experimental Dermatology 30, no. 3 (2021): 319–336.
- 25Q. Zhang, H. Wang, C. Ran, et al., “Anti-Inflammatory Effects of Amarogentin on 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis-Like Mice and in HaCat Cells,” International Wound Journal Animal Models and Experimental Medicine 6, no. 3 (2023): 255–265.
- 26S. K. Stacey and M. McEleney, “Topical Corticosteroids: Choice and Application,” American Family Physician 103, no. 6 (2021): 337–343.
- 27D. E. Cohen and N. Heidary, “Treatment of Irritant and Allergic Contact Dermatitis,” Dermatologic Therapy 17, no. 4 (2004): 334–340.
- 28J. I. Silverberg, A. Armstrong, A. Blauvelt, and K. Reich, “Assessment of Efficacy and Safety Outcomes Beyond Week 16 in Clinical Trials of Systemic Agents Used for the Treatment of Moderate to Severe Atopic Dermatitis in Combination With Topical Corticosteroids,” American Journal of Clinical Dermatology 24, no. 6 (2023): 913–925.
- 29J. Hwang-Bo, K. Veerappan, H. Moon, et al., “Parnassin, a Novel Therapeutic Peptide, Alleviates Skin Lesions in a DNCB-Induced Atopic Dermatitis Mouse Model,” Biomedicines 11, no. 5 (2023): 1389.
- 30I. J. Moon, M. R. Yun, H. K. Yoon, et al., “Treatment of Atopic Dermatitis Using Non-Thermal Atmospheric Plasma in an Animal Model,” Scientific Reports 11, no. 1 (2021): 16091.
- 31J. S. Oh, G. S. Seong, Y. D. Kim, and C. SY, “Deacetylasperulosidic Acid Ameliorates Pruritus, Immune Imbalance, and Skin Barrier Dysfunction in 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis NC/Nga Mice,” International Journal of Molecular Sciences 23, no. 1 (2021): 226.
- 32Y. Yamamura, C. Nakashima, and A. Otsuka, “Interplay of Cytokines in the Pathophysiology of Atopic Dermatitis: Insights From Murin Models and Human,” Front Med (Lausanne) 11 (2024): 1342176.
- 33H. He and E. J. A. K. Guttman-Yassky, “Inhibitors for Atopic Dermatitis: An Update,” American Journal of Clinical Dermatology 20, no. 2 (2019): 181–192.
- 34S. Y. Lee, N. J. Park, J. Jegal, et al., “Suppression of DNCB-Induced Atopic Skin Lesions in Mice by Wikstroemia Indica Extract,” Nutrients 12, no. 1 (2020): 173.
- 35L. O'Mahony, M. Akdis, and C. A. Akdis, “Regulation of the Immune Response and Inflammation by Histamine and Histamine Receptors,” Journal of Allergy and Clinical Immunology 128, no. 6 (2011): 1153–1162.
- 36F. T. Liu, H. Goodarzi, and H. Y. Chen, “IgE, Mast Cells, and Eosinophils in Atopic Dermatitis,” Clinical Reviews in Allergy & Immunology 41, no. 3 (2011): 298–310.
- 37T. J. Won, B. Kim, Y. Lee, et al., “Therapeutic Potential of Lactobacillus Plantarum CJLP133 for House-Dust Mite-Induced Dermatitis in NC/Nga Mice,” Cellular Immunology 277, no. 1-2 (2012): 49–57.
- 38L. Lugović-Mihić, J. Meštrović-Štefekov, I. Potočnjak, et al., “Atopic Dermatitis: Disease Features, Therapeutic Options, and a Multidisciplinary Approach,” Life (Basel) 13, no. 6 (2023): 1419.
- 39M. H. Rohner, K. Thormann, S. Cazzaniga, et al., “Dupilumab Reduces Inflammation and Restores the Skin Barrier in Patients with Atopic Dermatitis,” Allergy 76, no. 4 (2021): 1268–1270.
- 40E. Hagforsen, M. Lampinen, A. Paivandy, et al., “Siramesine Causes Preferential Apoptosis of Mast Cells in Skin Biopsies From Psoriatic Lesions,” British Journal of Dermatology 177, no. 1 (2017): 179–187.
- 41A. D. Irvine, W. H. McLean, and D. Y. Leung, “Filaggrin Mutations Associated With Skin and Allergic Diseases,” New England Journal of Medicine 365, no. 14 (2011): 1315–1327.
- 42W. Peng and N. Novak, “Pathogenesis of Atopic Dermatitis,” Clinical and Experimental Allergy 45, no. 3 (2015): 566–574.
- 43H. S. Han, Y. G. Koh, J. K. Hong, Y. J. Roh, S. J. Seo, and K. Y. Park, “Adipose-Derived Stem Cell Exosomes for Treatment of Dupilumab-Related Facial Redness in Patients With Atopic Dermatitis,” Journal of Dermatological Treatment 34, no. 1 (2023): 2220444.
- 44M. Sasakura, H. Urakami, K. Tachibana, et al., “Topical Application of Activator Protein-1 Inhibitor T-5224 Suppresses Inflammation and Improves Skin Barrier Function in a Murine Atopic Dermatitis-Like Dermatitis,” Allergology International 73, no. 2 (2024): 323–331.
- 45A. B. Pavel, T. Song, H. J. Kim, et al., “Oral Janus Kinase/SYK Inhibition (ASN002) Suppresses Inflammation and Improves Epidermal Barrier Markers in Patients with Atopic Dermatitis,” Journal of Allergy and Clinical Immunology 144, no. 4 (2019): 1011–1024.
- 46K. Sitko, M. Starke, and S. Tukaj, “Heat Shock Protein 90 (Hsp90) Inhibitor STA-9090 (Ganetespib) Ameliorates Inflammation in a Mouse Model of Atopic Dermatitis,” Cell Stress & Chaperones 28, no. 6 (2023): 935–942.