Natural killer (NK) cell is a type of immune cell and is known to be particularly responsible for innate immunity such as anti-cancer immunity, defense mechanisms against infections, and secretion of various cytokines and chemokines for increasing recruitment of other immune cells. In this study, we investigated the potentials of NK-enriched lymphocytes (NKEL) conditioned media (CM) on skin care for cosmeceutical compositions. Various cytokines of NKEL CM can improve wound healing through epithelial-mesenchymal transition (EMT) by increasing KLKs (kallikreins) and reduce metalloproteinase (MMP)-1 and MMP-2 to inhibit wrinkle formation. Our results suggest that NKEL CM which has various cytokines promotes up-regulation of cell migration and KLKs and down-regulation of MMP-1 and MMP-2 by stimulating HaCaT keratinocytes migration. Therefore, NKEL CM can be used as a cosmetic composition that can play a role in skin regeneration and anti-aging.
References
[1]
Global Insight, Inc. (2009) A Study of the European Cosmetics Industry (2007). DG Internal Market, Industry, Entrepreneurship and SMEs, Geneva, Switzerland.
[2]
Kumar, S. (2005) Exploratory Analysis of Global Cosmetic Industry: Major Players, Technology and Market Trends. Technovation, 25, 1263-1272. https://doi.org/10.1016/j.technovation.2004.07.003
[3]
Dureja, H., Kaushik, D., Gupta, M., Kumar, V. and Lather, V. (2005) Cosmeceuticals: An Emerging Concept. Indian Journal of Pharmacology, 37, 155-159. https://doi.org/10.4103/0253-7613.16211
[4]
Sgarbieri, V.C. and Pacheco, M.T.B. (2017) Healthy Human Aging: Intrinsic and Environmental Factors. Brazilian Journal of Food Technology, 20, e2017007. https://doi.org/10.1590/1981-6723.00717
[5]
Kabashima, K., Honda, T., Ginhoux, F. and Egawa, G. (2019) The Immunological Anatomy of the Skin. Nature Reviews Immunology, 19, 19-30. https://doi.org/10.1038/s41577-018-0084-5
[6]
Verdier-Sévrain, S. and Bonté, F. (2007) Skin Hydration: A Review on Its Molecular Mechanisms. Journal of Cosmetic Dermatology, 6, 75-82. https://doi.org/10.1111/j.1473-2165.2007.00300.x
[7]
Nafisi, S. and Maibach, H.I. (2018) Chapter 3—Skin Penetration of Nanoparticles. In: Emerging Nanotechnologies in Immunology, Elsevier, 47-88. https://doi.org/10.1016/B978-0-323-40016-9.00003-8
[8]
Del Rosso, J.Q. and Levin, J. (2011) The Clinical Relevance of Maintaining the Functional Integrity of the Stratum Corneum in Both Healthy and Disease-Affected Skin. The Journal of Clinical and Aesthetic Dermatology, 4, 22-42.
[9]
Amarya, S., Singh, K. and Sabharwal, M. (2018) Chapter 1—Ageing Process and Physiological Changes. In: D’Onofrio, G., Greco, A. and Sancarlo, D., Eds., Gerontology, IntechOpen, London, UK, 3-24. https://doi.org/10.5772/intechopen.76249
Ramos-e-Silva, M. and da Silva Carneiro, S.C. (2007) Elderly Skin and Its Rejuvenation: Products and Procedures for the Aging Skin. Journal of Cosmetic Dermatology, 6, 40-50. https://doi.org/10.1111/j.1473-2165.2007.00289.x
[12]
Kontos, C.K. and Scorilas, A. (2012) Kallikrein-Related Peptidases (KLKs): A Gene Family of Novel Cancer Biomarkers. Clinical Chemistry and Laboratory Medicine, 50, 1877-1891. https://doi.org/10.1515/cclm-2012-0247
[13]
Prassas, I., Eissa, A., Poda, G. and Diamandis, E.P. (2015) Unleashing the Therapeutic Potential of Human Kallikrein-Related Serine Proteases. Nature Reviews Drug Discovery, 14, 183-202. https://doi.org/10.1038/nrd4534
[14]
Kalinska, M., Meyer-Hoffert, U., Kantyka, T. and Potempa, J. (2016) Kallikreins—The Melting Pot of Activity and Function. Biochimie, 122, 270-282. https://doi.org/10.1016/j.biochi.2015.09.023
[15]
Miyai, M., Matsumoto, Y., Yamanishi, H., Yamamoto-Tanaka, M., Tsuboi, R. and Hibino, T. (2014) Keratinocyte-Specific Mesotrypsin Contributes to the Desquamation Process via Kallikrein Activation and LEKTI Degradation. Journal of Investigative Dermatology, 134, 1665-1674. https://doi.org/10.1038/jid.2014.3
[16]
Nauroy, P. and Nyström, A. (2019) Kallikreins: Essentialepidermal Messengers for Regulation of the Skin Microenvironment during Homeostasis, Repair and Disease. Matrix Biology Plus, 6-7, Article ID: 100019. https://doi.org/10.1016/j.mbplus.2019.100019
[17]
Rodríguez, D., Morrison, C.J., Overall, C.M., Rodríguez, D., Morrison, C.J. and Overall, C.M. (2010) Matrix Metalloproteinases: What Do They Not Do? New Substrates and Biological Roles Identified by Murine Models and Proteomics. Biochimica et Biophysica Acta, 1803, 39-54. https://doi.org/10.1016/j.bbamcr.2009.09.015
[18]
Zakiyanov, O., Kalousová, M., Zima, T. and Tesař, V. (2019) Matrix Metalloproteinases in Renal Diseases: A Critical Appraisal. Kidney and Blood Pressure Research, 44, 298-330. https://doi.org/10.1159/000499876
[19]
Freitas-Rodríguez, S., Folgueras, A.R. and López-Otín, C. (2017) The Role of Matrix Metalloproteinases in Aging: Tissue Remodeling and Beyond. Biochimica et Biophysica Acta, 1864, 2015-2025. https://doi.org/10.1016/j.bbamcr.2017.05.007
[20]
Tokuhara, C.K., Santesso, M.R., de Oliveira, G.S.N., da Silva Ventura, T.M., Doyama, J.T., Zambuzzi, W.F. and de Oliveira, R.C. (2019) Updating the Role of Matrix Metalloproteinases in Mineralized Tissue and Related Diseases. Journal of Applied Oral Science, 27, e20180596. https://doi.org/10.1590/1678-7757-2018-0596
[21]
Cole, M.A., Quan, T., Voorhees, J.J. and Fisher, G.J. (2018) Extracellular Matrix Regulation of Fibroblast Function: Redefining Our Perspective on Skin Aging. Journal of Cell Communication and Signaling, 12, 35-43. https://doi.org/10.1007/s12079-018-0459-1
[22]
Pittayapruek, P., Meephansan, J., Prapapan, O., Komine, M. and Ohtsuki, M. (2016) Role of Matrix Metalloproteinases in Photoaging and Photocarcinogenesis. International Journal of Molecular Sciences, 17, 868. https://doi.org/10.3390/ijms17060868
[23]
Vivier, E., Raulet, D.H., Moretta, A., Caligiuri, M.A., Zitvogel, L., Lanier, L.L., Yokoyama, W.M. and Ugolini, S. (2011) Innate or Adaptive Immunity? The Example of Natural Killer Cells. Science, 331, 44-49. https://doi.org/10.1126/science.1198687
[24]
Zucchini, N., Crozat, K., Baranek, T., Robbins, S.H., Altfeld, M. and Dalod, M. (2008) Natural Killer Cells in Immunodefense against Infective Agents. Expert Review of Anti-infective Therapy, 6, 867-885. https://doi.org/10.1586/14787210.6.6.867
[25]
Almishri, W., Santodomingo-Garzon, T., Le, T., Stack, D., Mody, C.H. and Swain, M.G. (2016) TNFα Augments Cytokine-Induced NK Cell IFNγ Production through TNFR2. Journal of Innate Immunity, 8, 617-629. https://doi.org/10.1159/000448077
[26]
Justus, C.R., Leffler, N., Ruiz-Echevarria, M. and Yang, L.V. (2014) In Vitro Cell Migration and Invasion Assays. Journal of Visualized Experiments, 88, e51046. https://doi.org/10.3791/51046
[27]
Komatsu, N., Takata, M., Otsuki, N., Toyama, T., Ohka, R., Takehara, K. and Saijoh, K. (2003) Expression and Localization of Tissue Kallikrein mRNAs in Human Epidermis and Appendages. Journal of Investigative Dermatology, 121, 542-549. https://doi.org/10.1046/j.1523-1747.2003.12363.x
[28]
Trojahn, C., Dobos, G., Lichterfeld, A., Blume-Peytavi, U. and Kottner, J. (2015) Characterizing Facial Skin Ageing in Humans: Disentangling Extrinsic from Intrinsic Biological Phenomena. BioMed Research International, 2015, Article ID: 318586. https://doi.org/10.1155/2015/318586
[29]
Krutmann, J., Bouloc, A., Sore, G., Bernard, B.A. and Passeron, T. (2017) The Skin Aging Exposome. Journal of Dermatological Science, 85, 152-161. https://doi.org/10.1016/j.jdermsci.2016.09.015
[30]
Wu, S.-Y., Fu, T., Jiang, Y.-Z. and Shao, Z.-M. (2020) Natural Killer Cells in Cancer Biology and Therapy. Molecular Cancer, 19, Article No. 120. https://doi.org/10.1186/s12943-020-01238-x
[31]
van Erp, E.A., van Kampen, M.R., van Kasteren, P.B. and de Wit, J. (2019) Viral Infection of Human Natural Killer Cells. Viruses, 11, 243. https://doi.org/10.3390/v11030243
[32]
Brown, G.C. (2015) Living Too Long. EMBO Reports, 16, 137-141. https://doi.org/10.15252/embr.201439518
[33]
Ganceviciene, R., Liakou, A.I., Theodoridis, A., Makrantonaki, E. and Zouboulis, C.C. (2012) Skin Anti-Aging Strategies. Dermato-Endocrinology, 4, 308-319. https://doi.org/10.4161/derm.22804
[34]
Low, Q.E.H., Drugea, I.A., Duffner, L.A., Quinn, D.G., Cook, D.N., Rollins, B.J., Kovacs, E.J. and DiPietro, L.A. (2001) Wound Healing in MIP-1α-/-and MCP-1-/-Mice. American Journal of Pathology, 159, 457-463. https://doi.org/10.1016/S0002-9440(10)61717-8
[35]
Michopoulou, A. and Roussselle, P. (2015) How Do Epidermal Matrix Metalloproteinases Support Re-Epithelialization during Skin Healing? European Journal of Dermatology, 25, 33-42. https://doi.org/10.1684/ejd.2015.2553
[36]
Kanno, E., Tanno, H., Masaki, A., Sasaki, A., Sato, N., Goto, M., Shisai, M., Yamaguchi, K., Takagi, N., Shoji, M., Kitai, Y., Sato, K., Kasamatsu, J., Ishii, K., Miyasaka, T., Kawakami, K., Imai, Y., Iwakura, Y., Maruyama, R., Tachi, M. and Kawakami, K. (2019) Defect of Interferon γ Leads to Impaired Wound Healing through Prolonged Neutrophilic Inflammatory Response and Enhanced MMP-2 Activation. International Journal of Molecular Sciences, 20, 5657. https://doi.org/10.3390/ijms20225657
[37]
Park, S.L., Chung, T.-W., Kim, S., Hwang, B., Kim, J.M., Lee, H.M., Cha, H.-J., Seo, Y., Choe, S.Y., Ha, K.-T., Kim, G., Yun, S.-J., Park, S.-S., Choi, Y.H., Kim, B.K., Kim, W.T., Cha, E.-J., Patterson, C., Kim, W.-J. and Moon, S.-K. (2017) HSP70-1 Is Required for Interleukin-5-Induced Angiogenic Responses through eNOS Pathway. Scientific Reports, 7, Article No. 44687. https://doi.org/10.1038/srep44687
[38]
Lan, C.-C.E., Wu, C.-S., Huang, S.-M., Wu, I.-H. and Chen, G.-S. (2013) High-Glucose Environment Enhanced Oxidative Stress and Increased Interleukin-8 Secretion from Keratinocytes: New Insights into Impaired Diabetic Wound Healing. Diabetes, 62, 2530-2538. https://doi.org/10.2337/db12-1714
[39]
Hänel, K.H., Cornelissen, C., Lüscher, B. and Baron, J.M. (2013) Cytokines and the Skin Barrier. International Journal of Molecular Sciences, 14, 6720-6745. https://doi.org/10.3390/ijms14046720
[40]
Zhao, Y., Shimizu, T., Nishihira, J., Koyama, Y., Kushibiki, T., Honda, A., Watanabe, H., Abe, R., Tabata, Y. and Shimizu, H. (2005) Tissue Regeneration Using Macrophage Migration Inhibitory Factor-Impregnated Gelatin Microbeads in Cutaneous Wounds. American Journal of Pathology, 167, 1519-1529. https://doi.org/10.1016/S0002-9440(10)61238-2
[41]
Marks, R. (2004) The Stratum Corneum Barrier: The Final Frontier. The Journal of Nutrition, 134, 2017S-2021S. https://doi.org/10.1093/jn/134.8.2017S
[42]
Kim, M. and Park, H.J. (2016) Chapter 3—Molecular Mechanisms of Skin Aging and Rejuvenation. In: Shiomi, N., Ed., Molecular Mechanisms of the Aging Process and Rejuvenation, IntechOpen., London, UK, 57-76. https://doi.org/10.5772/62983
[43]
Chen, J.-Q., Liang, B.-H., Li, H.-P., Mo, Z.-Y. and Zhu, H.-L. (2019) Roles of Kallikrein-Related Peptidase in Epidermal Barrier Function and Related Skin Diseases. International Journal of Dermatology and Venereology, 2, 150-155. https://doi.org/10.1097/JD9.0000000000000036
[44]
Larouche, J., Sheoran, S., Maruyama, K. and Martino, M.M. (2018) Immune Regulation of Skin Wound Healing: Mechanisms and Novel Therapeutic Targets. Advances in Wound Care, 7, 209-231. https://doi.org/10.1089/wound.2017.0761
[45]
Falanga, V. (2005) Wound Healing and Its Impairment in the Diabetic Foot. The Lancet, 366, 1736-1743. https://doi.org/10.1016/S0140-6736(05)67700-8
[46]
Stone, R.C., Pastar, I., Ojeh, N., Chen, V., Liu, S., Garzon, K.I. and Tomic-Canic, M. (2016) Epithelial-Mesenchymal Transition in Tissue Repair and Fibrosis. Cell and Tissue Research, 365, 495-506. https://doi.org/10.1007/s00441-016-2464-0
[47]
Kuwahara, M., Hatoko, M., Tada, H. and Tanaka, A. (2001) E-Cadherin Expression in Wound Healing of Mouse Skin. Journal of Cutaneous Pathology, 28, 191-199. https://doi.org/10.1034/j.1600-0560.2001.028004191.x
[48]
Gloushankova, N.A., Rubtsova, S.N. and Zhitnyak, I.Y. (2017) Cadherin-Mediated Cell-Cell Interactions in Normal and Cancer Cells. Tissue Barriers, 5, e1356900. https://doi.org/10.1080/21688370.2017.1356900
[49]
Yilmaz, M. and Christofori, G. (2009) EMT, the Cytoskeleton, and Cancer Cell Invasion. Cancer and Metastasis Reviews, 28, 15-33. https://doi.org/10.1007/s10555-008-9169-0
[50]
Lamouille, S., Xu, J. and Derynck, R. (2014) Molecular Mechanisms of Epithelial-Mesenchymal Transition. Nature Reviews Molecular Cell Biology, 15, 178-196. https://doi.org/10.1038/nrm3758
[51]
Varani, J., Dame, M.K., Rittie, L., Fligiel, S.E.G., Kang, S., Fisher, G.J. and Voorhees, J.J. (2006) Decreased Collagen Production in Chronologically Aged Skin: Roles of Age-Dependent Alteration in Fibroblast Function and Defective Mechanical Stimulation. American Journal of Pathology, 168, 1861-1868. https://doi.org/10.2353/ajpath.2006.051302
[52]
Shoulders, M.D. and Raines, R.T. (2009) Collagen Structure and Stability. Annual Review of Biochemistry, 78, 929-958. https://doi.org/10.1146/annurev.biochem.77.032207.120833
[53]
Kular, J.K., Basu, S. and Sharma, R.I. (2014) The Extracellular Matrix: Structure, Composition, Age-Related Differences, Tools for Analysis and Applications for Tissue Engineering. Journal of Tissue Engineering, 5, 2041731414557112. https://doi.org/10.1177/2041731414557112
[54]
Van Doren, S.R. (2015) Matrix Metalloproteinase Interactions with Collagen and Elastin. Matrix Biology, 44-46, 224-231. https://doi.org/10.1016/j.matbio.2015.01.005
[55]
Hu, X. and Beeton, C. (2010) Detection of Functional Matrix Metalloproteinases by Zymography. Journal of Visualized Experiments, 45, e2445. https://doi.org/10.3791/2445
[56]
Gyulai, R., Hunyadi, J., Kenderessy-Szabó, A., Kemény, L. and Dobozy, A. (1994) Chemotaxis of Freshly Separated and Cultured Human Keratinocytes. Clinical and Experimental Dermatology, 19, 309-311. https://doi.org/10.1111/j.1365-2230.1994.tb01201.x
[57]
Takada, K., Komine-Aizawa, S., Hirohata, N., Trinh, Q.D., Nishina, A., Kimura, H. and Hayakawa, S. (2017) Poly I:C Induces Collective Migration of HaCaT Keratinocytes via IL-8. BMC Immunology, 18, Article No. 19. https://doi.org/10.1186/s12865-017-0202-3
[58]
Abe, R., Shimizu, T., Ohkawara, A. and Nishihira, J. (2000) Enhancement of Macrophage Migration Inhibitory Factor (MIF) Expression in Injured Epidermis and Cultured Fibroblasts. Biochimica et Biophysica Acta, 1500, 1-9. https://doi.org/10.1016/S0925-4439(99)00080-0
[59]
Czekay, R.-P., Wilkins-Port, C.E., Higgins, S.P., Freytag, J., Overstreet, J.M., Klein, R.M., Higgins, C.E., Samarakoon, R. and Higgins, P.J. (2011) PAI-1: An Integrator of Cell Signaling and Migration. International Journal of Cell Biology, 2011, Article ID: 562481. https://doi.org/10.1155/2011/562481
[60]
Providence, K.M., Higgins, S.P., Mullen, A., Battista, A., Samarakoon, R., Higgins, C.E., Wilkins-Port, C.E. and Higgins, P.J. (2008) SERPINE1 (PAI-1) Is Deposited into Keratinocyte Migration “Trails” and Required for Optimal Monolayer Wound Repair. Archives of Dermatological Research, 300, 303-310. https://doi.org/10.1007/s00403-008-0845-2
[61]
Simone, T.M., Longmate, W.M., Law, B.K. and Higgins, P.J. (2015) Targeted Inhibition of PAI-1 Activity Impairs Epithelial Migration and Wound Closure Following Cutaneous Injury. Advances in Wound Care, 4, 321-328. https://doi.org/10.1089/wound.2014.0611
[62]
Seeger, M.A. and Paller, A.S. (2015) The Roles of Growth Factors in Keratinocyte Migration. Advances in Wound Care, 4, 213-224. https://doi.org/10.1089/wound.2014.0540
