每年出版 6 期
ISSN 打印: 1040-8401
ISSN 在线: 2162-6472
Indexed in
Human Defensins and Cathelicidins in the Skin: Beyond Direct Antimicrobial Properties
摘要
A cutaneous barrier defends the body against invading pathogenic microorganisms due to both innate and adaptive immunity. The innate immune system comprises hundreds of peptides/proteins, which have potent microbicidal activities at low concentrations. Among these microbicidal agents, an increasing body of research has suggested that a vast arsenal of antimicrobial peptides composed of defensins and cathelicidins are key players in cutaneous immunity. Mainly produced by phagocytes and epithelial cells, defensins and cathelicidins directly or indirectly kill a wide range of bacteria, fungi, and viruses. However, it is increasingly evident that these peptides not only act as endogenous antibiotics but also display additional roles, such as regulation of inflammatory and immune responses, chemoattracting immune or inflammatory cells to wound or infection/inflammation sites, acceleration of angiogenesis, promotion of wound healing, and reepithelization, and binding and neutralizing of lipopolysaccharides. Here, we review the skin-derived antimicrobial peptides with an emphasis on their role in skin immune responses. We present an overview of defensin and cathelicidin structure and expression, clarify their various functions beyond microbicidal properties, and describe their modes of action. Moreover, we discuss the roles of these peptides in skin diseases and highlight their possible use in near therapeutic development.
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Clancy N., Onwuneme C., Carroll A., McCarthy R., McKenna M. J., Murphy N., Molloy E. J., Vitamin D and neonatal immune function, The Journal of Maternal-Fetal & Neonatal Medicine, 26, 7, 2013. Crossref
-
Devine Deirdre A., Cosseau Celine, Host Defense Peptides in the Oral Cavity, in Advances in Applied Microbiology Volume 63, 63, 2008. Crossref
-
DIEFFENBACH CARL W., TRAMONT EDMUND C., PLAEGER SUSAN F., Innate (General or Nonspecific) Host Defense Mechanisms, in Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, 2010. Crossref
-
Hegedüs Nikoletta, Marx Florentine, Antifungal proteins: More than antimicrobials?, Fungal Biology Reviews, 26, 4, 2013. Crossref
-
Nagaoka I., Niyonsaba F., Tsutsumi-Ishii Y., Tamura H., Hirata M., Evaluation of the effect of human -defensins on neutrophil apoptosis, International Immunology, 20, 4, 2008. Crossref
-
Zheng Yan, Niyonsaba François, Ushio Hiroko, Ikeda Shigaku, Nagaoka Isao, Okumura Ko, Ogawa Hideoki, Microbicidal protein psoriasin is a multifunctional modulator of neutrophil activation, Immunology, 124, 3, 2008. Crossref
-
Zheng Y., Niyonsaba F., Ushio H., Nagaoka I., Ikeda S., Okumura K., Ogawa H., Cathelicidin LL-37 induces the generation of reactive oxygen species and release of human α-defensins from neutrophils, British Journal of Dermatology, 157, 6, 2007. Crossref
-
Türkoğlu Oya, Gürkan Ali, Emingil Gülnur, Afacan Beral, Töz Hüseyin, Kütükçüler Necil, Atilla Gül, Are antimicrobial peptides related to cyclosporine A-induced gingival overgrowth?, Archives of Oral Biology, 60, 3, 2015. Crossref
-
Hattori F., Kiatsurayanon C., Okumura K., Ogawa H., Ikeda S., Okamoto K., Niyonsaba F., The antimicrobial protein S100A7/psoriasin enhances the expression of keratinocyte differentiation markers and strengthens the skin's tight junction barrier, British Journal of Dermatology, 171, 4, 2014. Crossref
-
Archer C. B., Functions of the Skin, in Rook's Textbook of Dermatology, 2010. Crossref
-
Baroli Biancamaria, Penetration of nanoparticles and nanomaterials in the skin: Fiction or reality?, Journal of Pharmaceutical Sciences, 99, 1, 2010. Crossref
-
Nagaoka Isao, Suzuki Kaori, Niyonsaba François, Tamura Hiroshi, Hirata Michimasa, Modulation of Neutrophil Apoptosis by Antimicrobial Peptides, ISRN Microbiology, 2012, 2012. Crossref
-
McGrath J. A., Uitto J., Anatomy and Organization of Human Skin, in Rook's Textbook of Dermatology, 2010. Crossref
-
Cornelissen Christian, Lüscher-Firzlaff Juliane, Baron Jens Malte, Lüscher Bernhard, Signaling by IL-31 and functional consequences, European Journal of Cell Biology, 91, 6-7, 2012. Crossref
-
Schwalfenberg Gerry K., A review of the critical role of vitamin D in the functioning of the immune system and the clinical implications of vitamin D deficiency, Molecular Nutrition & Food Research, 55, 1, 2011. Crossref
-
Kamen Diane L., Tangpricha Vin, Vitamin D and molecular actions on the immune system: modulation of innate and autoimmunity, Journal of Molecular Medicine, 88, 5, 2010. Crossref
-
Niyonsaba F., Suzuki A., Ushio H., Nagaoka I., Ogawa H., Okumura K., The human antimicrobial peptide dermcidin activates normal human keratinocytes, British Journal of Dermatology, 160, 2, 2009. Crossref
-
Cork Michael J., Danby Simon G., Vasilopoulos Yiannis, Hadgraft Jonathan, Lane Majella E., Moustafa Manar, Guy Richard H., MacGowan Alice L., Tazi-Ahnini Rachid, Ward Simon J., Epidermal Barrier Dysfunction in Atopic Dermatitis, Journal of Investigative Dermatology, 129, 8, 2009. Crossref
-
Murakami T., Obata T., Kuwahara-Arai K., Tamura H., Hiramatsu K., Nagaoka I., Antimicrobial cathelicidin polypeptide CAP11 suppresses the production and release of septic mediators in D-galactosamine-sensitized endotoxin shock mice, International Immunology, 21, 8, 2009. Crossref
-
Tarasov V. A., Khadeeva N. V., Mel’nik V. A., Ezhova T. A., Shestakov S. V., The Atlg12860 gene of Arabidopsis thaliana determines cathelicidin-like antimicrobial activity, Doklady Biological Sciences, 427, 1, 2009. Crossref
-
Smithrithee Rithee, Niyonsaba François, Kiatsurayanon Chanisa, Ushio Hiroko, Ikeda Shigaku, Okumura Ko, Ogawa Hideoki, Human β-defensin-3 increases the expression of interleukin-37 through CCR6 in human keratinocytes, Journal of Dermatological Science, 77, 1, 2015. Crossref
-
Kanazawa Kazo, Okumura Ko, Ogawa Hideoki, Niyonsaba François, An antimicrobial peptide with angiogenic properties, AG-30/5C, activates human mast cells through the MAPK and NF-κB pathways, Immunologic Research, 64, 2, 2016. Crossref
-
Pasupuleti Mukesh, Schmidtchen Artur, Malmsten Martin, Antimicrobial peptides: key components of the innate immune system, Critical Reviews in Biotechnology, 32, 2, 2012. Crossref
-
Baroni Adone, Buommino Elisabetta, De Gregorio Vincenza, Ruocco Eleonora, Ruocco Vincenzo, Wolf Ronni, Structure and function of the epidermis related to barrier properties, Clinics in Dermatology, 30, 3, 2012. Crossref
-
Méndez-Samperio Patricia, The human cathelicidin hCAP18/LL-37: A multifunctional peptide involved in mycobacterial infections, Peptides, 31, 9, 2010. Crossref
-
Iaccio Annalisa, Cattaneo Fabio, Mauro Martina, Ammendola Rosario, FPRL1-mediated induction of superoxide in LL-37-stimulated IMR90 human fibroblast, Archives of Biochemistry and Biophysics, 481, 1, 2009. Crossref
-
Benson Kathleen F., Carter Steve G., Patterson Kelly M., Patel Dilip, Jensen Gitte S., A novel extract from bovine colostrum whey supports anti-bacterial and anti-viral innate immune functions in vitro and in vivo, Preventive Medicine, 54, 2012. Crossref
-
Niyonsaba François, Hattori Fumihiro, Maeyama Kaoru, Ogawa Hideoki, Okamoto Kikuhiko, Induction of a microbicidal protein psoriasin (S100A7), and its stimulatory effects on normal human keratinocytes, Journal of Dermatological Science, 52, 3, 2008. Crossref
-
Fukuyama Tomoki, Ganchingco Joy Rachel, Bäumer Wolfgang, Demonstration of rebound phenomenon following abrupt withdrawal of the JAK1 inhibitor oclacitinib, European Journal of Pharmacology, 794, 2017. Crossref
-
Lüthje Petra, Brauner Annelie, Novel Strategies in the Prevention and Treatment of Urinary Tract Infections, Pathogens, 5, 1, 2016. Crossref
-
NIYONSABA FRANÇOIS, Novel Insight Into the Role of Antimicrobial (Host Defense) Peptides/Proteins in Human Skin Diseases, Juntendo Medical Journal, 62, 2, 2016. Crossref
-
Niyonsaba F., Kiatsurayanon C., Ogawa H., The role of human β-defensins in allergic diseases, Clinical & Experimental Allergy, 46, 12, 2016. Crossref
-
Haisma Elisabeth M., Rietveld Marion H., de Breij Anna, van Dissel Jaap T., El Ghalbzouri Abdoelwaheb, Nibbering Peter H., Cole Alexander M, Inflammatory and Antimicrobial Responses to Methicillin-Resistant Staphylococcus aureus in an In Vitro Wound Infection Model, PLoS ONE, 8, 12, 2013. Crossref
-
Fraisier Christophe, Papa Anna, Granjeaud Samuel, Hintzen Rogier, Martina Byron, Camoin Luc, Almeras Lionel, Wang Tian, Cerebrospinal Fluid Biomarker Candidates Associated with Human WNV Neuroinvasive Disease, PLoS ONE, 9, 4, 2014. Crossref
-
Foulke Galen T., Nelson Amanda M., Immunology of Acne, in Clinical and Basic Immunodermatology, 2017. Crossref
-
Yanashima Kensuke, Chieosilapatham Panjit, Yoshimoto Eri, Okumura Ko, Ogawa Hideoki, Niyonsaba François, Innate defense regulator IDR-1018 activates human mast cells through G protein-, phospholipase C-, MAPK- and NF-ĸB-sensitive pathways, Immunologic Research, 65, 4, 2017. Crossref
-
Olli Sudar, Rangaraj Nandini, Nagaraj Ramakrishnan, Chakravortty Dipshikha, Effect of Selectively Introducing Arginine and D-Amino Acids on the Antimicrobial Activity and Salt Sensitivity in Analogs of Human Beta-Defensins, PLoS ONE, 8, 9, 2013. Crossref
-
Niyonsaba François, Kiatsurayanon Chanisa, Chieosilapatham Panjit, Ogawa Hideoki, Friends or Foes? Host defense (antimicrobial) peptides and proteins in human skin diseases, Experimental Dermatology, 26, 11, 2017. Crossref
-
Cherwonogrodzky John W., Barabé Nicole D., Grigat Michelle L., Lee William E., Poirier Robert T., Jager Scott J., Berger Bradley J., Pasetti M. F., Thermostable Cross-Protective Subunit Vaccine against Brucella Species, Clinical and Vaccine Immunology, 21, 12, 2014. Crossref
-
ZHOU Xinyi, ZHANG Peng, WANG Qian, XIA Sisi, JI Ning, DING Yi, WANG Qi, 25-Hydroxyvitamin D<sub>3</sub> Alleviates Experimental Periodontitis via Promoting Expression of Cathelicidin in Mice with Type 2 Diabetic Mellitus, Journal of Nutritional Science and Vitaminology, 64, 5, 2018. Crossref
-
Lee Mi Young, Shin Eun, Kim Hyunchul, Kwak In Suk, Choi Younghee, Interleukin-31, Interleukin-31RA, and OSMR Expression Levels in Post-burn Hypertrophic Scars, Journal of Pathology and Translational Medicine, 52, 5, 2018. Crossref
-
Niyonsaba François, Madera Laurence, Afacan Nicole, Okumura Ko, Ogawa Hideoki, Hancock Robert E. W., The innate defense regulator peptides IDR-HH2, IDR-1002, and IDR-1018 modulate human neutrophil functions, Journal of Leukocyte Biology, 94, 1, 2013. Crossref
-
Zhao Yonghui, Xie Zili, Feng Jing, Li Wenxin, Cao Zhijian, Wu Yingliang, Pharmacological characterization of human beta-defensins 3 and 4 on potassium channels: Evidence of diversity in beta-defensin-potassium channel interactions, Peptides, 108, 2018. Crossref
-
Fruitwala Saahil, El-Naccache Darine W., Chang Theresa L., Multifaceted immune functions of human defensins and underlying mechanisms, Seminars in Cell & Developmental Biology, 88, 2019. Crossref
-
Guttman-Yassky Emma, Lowes Michelle A., Fuentes-Duculan Judilyn, Zaba Lisa C., Cardinale Irma, Nograles Kristine E., Khatcherian Artemis, Novitskaya Inna, Carucci John A., Bergman Reuven, Krueger James G., Low Expression of the IL-23/Th17 Pathway in Atopic Dermatitis Compared to Psoriasis, The Journal of Immunology, 181, 10, 2008. Crossref
-
YANASHIMA KENSUKE, CHIEOSILAPATHAM PANJIT, YOSHIMOTO ERI, OKUMURA KO, OGAWA HIDEOKI, NIYONSABA FRANÇOIS, Innate Defense Regulator IDR-1018 Activates Human Mast Cells Through G Protein-, Phospholipase C-, MAPK- and NF-κB-Sensitive Pathways, Juntendo Medical Journal, 65, 1, 2019. Crossref
-
KANAZAWA KAZO, OKUMURA KO, OGAWA HIDEOKI, NIYONSABA FRANCOIS, An Antimicrobial Peptide with Angiogenic Properties, AG-30/5C, Activates Human Mast Cells Through the MAPK and NF-κB Pathways, Juntendo Medical Journal, 65, 1, 2019. Crossref
-
Nguyen Alan V., Soulika Athena M., The Dynamics of the Skin’s Immune System, International Journal of Molecular Sciences, 20, 8, 2019. Crossref
-
Yang Chul-Su, Shin Dong-Min, Kim Ki-Hye, Lee Zee-Won, Lee Chul-Ho, Park Sung Goo, Bae Yun Soo, Jo Eun-Kyeong, NADPH Oxidase 2 Interaction with TLR2 Is Required for Efficient Innate Immune Responses to Mycobacteria via Cathelicidin Expression, The Journal of Immunology, 182, 6, 2009. Crossref
-
van Drongelen V., Haisma E. M., Out-Luiting J. J., Nibbering P. H., El Ghalbzouri A., Reduced filaggrin expression is accompanied by increasedStaphylococcus aureuscolonization of epidermal skin models, Clinical & Experimental Allergy, 44, 12, 2014. Crossref
-
Niyonsaba François, Ushio Hiroko, Hara Mutsuko, Yokoi Hidenori, Tominaga Mitsutoshi, Takamori Kenji, Kajiwara Naoki, Saito Hirohisa, Nagaoka Isao, Ogawa Hideoki, Okumura Ko, Antimicrobial Peptides Human β-Defensins and Cathelicidin LL-37 Induce the Secretion of a Pruritogenic Cytokine IL-31 by Human Mast Cells, The Journal of Immunology, 184, 7, 2010. Crossref
-
Dieffenbach Carl W, Tramont Edmund C., Innate (General or Nonspecific) Host Defense Mechanisms, in Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, 2015. Crossref
-
Jiang Yanyun, Tsoi Lam C., Billi Allison C., Ward Nicole L., Harms Paul W., Zeng Chang, Maverakis Emanual, Kahlenberg J. Michelle, Gudjonsson Johann E., Cytokinocytes: the diverse contribution of keratinocytes to immune responses in skin, JCI Insight, 5, 20, 2020. Crossref
-
Xie Kunhong, Su Guoqi, Chen Daiwen, Yu Bing, Huang Zhiqing, Yu Jie, Zheng Ping, Luo Yuheng, Yan Hui, Li Hua, He Jun, The immunomodulatory function of the porcine β-defensin 129: Alleviate inflammatory response induced by LPS in IPEC-J2 cells, International Journal of Biological Macromolecules, 188, 2021. Crossref
-
Wommack Andrew J., Robson Scott A., Wanniarachchi Yoshitha A., Wan Andrea, Turner Christopher J., Wagner Gerhard, Nolan Elizabeth M., NMR Solution Structure and Condition-Dependent Oligomerization of the Antimicrobial Peptide Human Defensin 5, Biochemistry, 51, 48, 2012. Crossref
-
Ferdowsi Shirin, Abbasi-Malati Zahra, Pourfathollah Ali Akbar, Leukocyte reduction filters as an alternative source of peripheral blood leukocytes for research, Hematology, Transfusion and Cell Therapy, 43, 4, 2021. Crossref
-
Takahashi Miho, Umehara Yoshie, Yue Hainan, Trujillo-Paez Juan Valentin, Peng Ge, Nguyen Hai Le Thanh, Ikutama Risa, Okumura Ko, Ogawa Hideoki, Ikeda Shigaku, Niyonsaba François, The Antimicrobial Peptide Human β-Defensin-3 Accelerates Wound Healing by Promoting Angiogenesis, Cell Migration, and Proliferation Through the FGFR/JAK2/STAT3 Signaling Pathway, Frontiers in Immunology, 12, 2021. Crossref
-
Brauner H, Lüthje P, Grünler J, Ekberg N R, Dallner G, Brismar K, Brauner A, Markers of innate immune activity in patients with type 1 and type 2 diabetes mellitus and the effect of the anti-oxidant coenzyme Q10 on inflammatory activity, Clinical and Experimental Immunology, 177, 2, 2014. Crossref
-
Almutairi Mikhlid, Almutairi Bader, Almutairi Mohammad, Parine Narasimha Reddy, Alrefaei Abdulwahed, Alanazi Mohammad, Semlali Abdelhabib, Human beta-defensin-1 rs2738047 polymorphism is associated with shisha smoking risk among Saudi population, Environmental Science and Pollution Research, 28, 31, 2021. Crossref
-
Huang Ling C., Redfern Rachel L., Narayanan Srihari, Reins Rose Y., McDermott Alison M., In Vitro Activity of Human β-Defensin 2 against Pseudomonas aeruginosa in the Presence of Tear Fluid , Antimicrobial Agents and Chemotherapy, 51, 11, 2007. Crossref
-
Holdbrook Daniel A., Singh Shalini, Choong Yeu Khai, Petrlova Jitka, Malmsten Martin, Bond Peter J., Verma Navin Kumar, Schmidtchen Artur, Saravanan Rathi, Influence of pH on the activity of thrombin-derived antimicrobial peptides, Biochimica et Biophysica Acta (BBA) - Biomembranes, 1860, 11, 2018. Crossref
-
Rhoads D.D., Wolcott R.D., Percival S.L., Biofilms in wounds: management strategies, Journal of Wound Care, 17, 11, 2008. Crossref
-
Ferdowsi Shirin, Pourfathollah Ali Akbar, Amiri Fatemeh, Rafiee Mohammad Hessam, Aghaei Afsaneh, Evaluation of anticancer activity of α-defensins purified from neutrophils trapped in leukoreduction filters, Life Sciences, 224, 2019. Crossref
-
Pashinjan A. G., Shahnovich A. A., Topical antibacterial medications for therapy of patient with acne, Vestnik dermatologii i venerologii, 93, 1, 2017. Crossref
-
Suwanchote Supaporn, Waitayangkoon Palapun, Chancheewa Bussabong, Inthanachai Thananya, Niwetbowornchai Nattarika, Edwards Steven W., Virakul Sita, Thammahong Arsa, Kiatsurayanon Chanisa, Rerknimitr Pawinee, Chiewchengchol Direkrit, Role of antimicrobial peptides in atopic dermatitis, International Journal of Dermatology, 61, 5, 2022. Crossref
-
Lüthje Petra, Brauner Hanna, Ramos Nubia L., Övregaard Amanda, Gläser Regine, Hirschberg Angelica Lindén, Aspenström Pontus, Brauner Annelie, Estrogen Supports Urothelial Defense Mechanisms, Science Translational Medicine, 5, 190, 2013. Crossref
-
Maisetta Giuseppantonio, Di Luca Mariagrazia, Esin Semih, Florio Walter, Brancatisano Franca Lisa, Bottai Daria, Campa Mario, Batoni Giovanna, Evaluation of the inhibitory effects of human serum components on bactericidal activity of human beta defensin 3, Peptides, 29, 1, 2008. Crossref
-
TEKUCHEVA L V, ZNAMENSKAYA L F, Experience of using peroral cosmetic products from the Emolium series in the complex therapy of children suffering from atopic dermatitis, Vestnik dermatologii i venerologii, 87, 2, 2011. Crossref
-
Kiatsurayanon Chanisa, Niyonsaba François, Smithrithee Rithee, Akiyama Toshihiro, Ushio Hiroko, Hara Mutsuko, Okumura Ko, Ikeda Shigaku, Ogawa Hideoki, Host Defense (Antimicrobial) Peptide, Human β-Defensin-3, Improves the Function of the Epithelial Tight-Junction Barrier in Human Keratinocytes, Journal of Investigative Dermatology, 134, 8, 2014. Crossref
-
Chopra Divya, Arens Rachel A., Amornpairoj Watcharee, Lowes Michelle A., Tomic-Canic Marjana, Strbo Natasa, Lev-Tov Hadar, Pastar Irena, Innate immunity and microbial dysbiosis in hidradenitis suppurativa – vicious cycle of chronic inflammation, Frontiers in Immunology, 13, 2022. Crossref
-
Kiatsurayanon Chanisa, Niyonsaba François, Chieosilapatham Panjit, Okumura Ko, Ikeda Shigaku, Ogawa Hideoki, Angiogenic peptide (AG)-30/5C activates human keratinocytes to produce cytokines/chemokines and to migrate and proliferate via MrgX receptors, Journal of Dermatological Science, 83, 3, 2016. Crossref
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Nguyen Toan The, Niyonsaba François, Ushio Hiroko, Akiyama Toshihiro, Kiatsurayanon Chanisa, Smithrithee Rithee, Ikeda Shigaku, Okumura Ko, Ogawa Hideoki, Interleukin-36 cytokines enhance the production of host defense peptides psoriasin and LL-37 by human keratinocytes through activation of MAPKs and NF-κB, Journal of Dermatological Science, 68, 1, 2012. Crossref
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Suzuki Kaori, Ohkuma Mari, Someya Akimasa, Mita Tomoya, Nagaoka Isao, Human Cathelicidin Peptide LL-37 Induces Cell Death in Autophagy-Dysfunctional Endothelial Cells, The Journal of Immunology, 208, 9, 2022. Crossref
-
Kurpet Katarzyna, Chwatko Grażyna, S100 Proteins as Novel Therapeutic Targets in Psoriasis and Other Autoimmune Diseases, Molecules, 27, 19, 2022. Crossref
-
Ramírez Thomé Saira, Ávila Curiel Beatriz, Hernández Huerta María T., Solórzano Mata Carlos, β-defensinas como posibles indicadores de la actividad inflamatoria en la enfermedad periodontal., Investigación Clínica, 63, 4, 2022. Crossref