Antimicrobial Peptide Loss, Except for LL-37, is not Characteristic of Atopic Dermatitis
DOI:
https://doi.org/10.2340/actadv.v103.9413Keywords:
Antimicrobial peptide, Atopic dermatitis, Skin barrier, PsoriasisAbstract
Atopic dermatitis is an inflammatory skin disease characterized by significant permeability barrier damage. Regulation and maintenance of permeability and antimicrobial skin barriers are strongly connected. There is a lack of comprehensive studies of the expression of all 5 major antimicrobial peptide functional groups in atopic dermatitis. The aim of this study was to investigate the major antimicrobial peptide functional groups in lesional atopic dermatitis, non-lesional atopic dermatitis, and healthy control samples, using real-time quantitative PCR and immunohistochemistry. Lesional psoriatic skin was also examined as a diseased control. No differences in mRNA levels were detected between non-lesional atopic dermatitis and healthy control skin, and, at the protein level, the only change was the significantly decreased LL-37 in non-lesional atopic dermatitis. In lesional atopic dermatitis, several antimicrobial peptides were significantly altered at the mRNA level, while, at the protein level, all antimicrobial peptides were significantly upregulated or unchanged, except for LL-37, which decreased, compared with healthy controls. Antimicrobial peptides were similarly elevated in lesional atopic dermatitis and lesional psoriatic skin, with somewhat higher expression in lesional psoriatic skin, except for LL-37. In conclusion, LL-37 was the only antimicrobial peptide that was impaired in both non-lesional and lesional atopic dermatitis, highlighting its potential pathogenetic or exacerbating role in the initial stages of the disease.
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Nguyen HLT, Trujillo-Paez JV, Umehara Y, Yue H, Peng G, Kiatsurayanon C, et al. Role of antimicrobial peptides in skin barrier repair in individuals with atopic dermatitis. Int J Mol Sci 2020; 21.
https://doi.org/10.3390/ijms21207607 DOI: https://doi.org/10.3390/ijms21207607
Beke G, Dajnoki Z, Kapitany A, Gaspar K, Medgyesi B, Poliska S, et al. Immunotopographical differences of human skin. Front Immunol 2018; 9: 424.
https://doi.org/10.3389/fimmu.2018.00424 DOI: https://doi.org/10.3389/fimmu.2018.00424
Borkowski AW, Gallo RL. The coordinated response of the physical and antimicrobial peptide barriers of the skin. J Invest Dermatol 2011; 131: 285-287.
https://doi.org/10.1038/jid.2010.360 DOI: https://doi.org/10.1038/jid.2010.360
Braff MH, Gallo RL. Antimicrobial peptides: an essential component of the skin defensive barrier. Curr Top Microbiol Immunol 2006; 306: 91-110.
https://doi.org/10.1007/3-540-29916-5_4 DOI: https://doi.org/10.1007/3-540-29916-5_4
Niyonsaba F, Kiatsurayanon C, Chieosilapatham P, Ogawa H. Friends or foes? Host defense (antimicrobial) peptides and proteins in human skin diseases. Exp Dermatol 2017; 26: 989-998.
https://doi.org/10.1111/exd.13314 DOI: https://doi.org/10.1111/exd.13314
Jenei A, Dajnoki Z, Medgyesi B, Gaspar K, Beke G, Kinyo A, et al. Apocrine gland-rich skin has a non-inflammatory IL-17-related immune milieu, that turns to inflammatory IL-17-mediated disease in hidradenitis suppurativa. J Invest Dermatol 2019; 139: 964-968.
https://doi.org/10.1016/j.jid.2018.10.020 DOI: https://doi.org/10.1016/j.jid.2018.10.020
Jenei A, Kallo G, Dajnoki Z, Gaspar K, Szegedi A, Kapitany A, et al. Detection of antimicrobial peptides in stratum corneum by mass spectrometry. Int J Mol Sci 2021; 22.
https://doi.org/10.3390/ijms22084233 DOI: https://doi.org/10.3390/ijms22084233
Yamasaki K, Gallo RL. Antimicrobial peptides in human skin disease. Eur J Dermatol 2008; 18: 11-21.
Clausen ML, Slotved HC, Krogfelt KA, Andersen PS, Agner T. In vivo expression of antimicrobial peptides in atopic dermatitis. Exp Dermatol 2016; 25: 3-9.
https://doi.org/10.1111/exd.12831 DOI: https://doi.org/10.1111/exd.12831
Yang G, Seok JK, Kang HC, Cho YY, Lee HS, Lee JY. Skin barrier abnormalities and immune dysfunction in atopic dermatitis. Int J Mol Sci 2020; 21.
https://doi.org/10.3390/ijms21082867 DOI: https://doi.org/10.3390/ijms21082867
Beck LA, Cork MJ, Amagai M, De Benedetto A, Kabashima K, Hamilton JD, et al. Type 2 inflammation contributes to skin barrier dysfunction in atopic dermatitis. JID Innov 2022; 2: 100131.
https://doi.org/10.1016/j.xjidi.2022.100131 DOI: https://doi.org/10.1016/j.xjidi.2022.100131
Egawa G, Kabashima K. Multifactorial skin barrier deficiency and atopic dermatitis: Essential topics to prevent the atopic march. J Allergy Clin Immunol 2016; 138: 350-358 e351.
https://doi.org/10.1016/j.jaci.2016.06.002 DOI: https://doi.org/10.1016/j.jaci.2016.06.002
Dorschner RA, Pestonjamasp VK, Tamakuwala S, Ohtake T, Rudisill J, Nizet V, et al. Cutaneous injury induces the release of cathelicidin anti-microbial peptides active against group A Streptococcus. J Invest Dermatol 2001; 117: 91-97.
https://doi.org/10.1046/j.1523-1747.2001.01340.x DOI: https://doi.org/10.1046/j.1523-1747.2001.01340.x
Aberg KM, Man MQ, Gallo RL, Ganz T, Crumrine D, Brown BE, et al. Co-regulation and interdependence of the mammalian epidermal permeability and antimicrobial barriers. J Invest Dermatol 2008; 128: 917-925.
https://doi.org/10.1038/sj.jid.5701099 DOI: https://doi.org/10.1038/sj.jid.5701099
Akiyama T, Niyonsaba F, Kiatsurayanon C, Nguyen TT, Ushio H, Fujimura T, et al. The human cathelicidin LL-37 host defense peptide upregulates tight junction-related proteins and increases human epidermal keratinocyte barrier function. J Innate Immun 2014; 6: 739-753.
https://doi.org/10.1159/000362789 DOI: https://doi.org/10.1159/000362789
Cau L, Williams MR, Butcher AM, Nakatsuji T, Kavanaugh JS, Cheng JY, et al. Staphylococcus epidermidis protease EcpA can be a deleterious component of the skin microbiome in atopic dermatitis. J Allergy Clin Immunol 2021; 147: 955-966 e916.
https://doi.org/10.1016/j.jaci.2020.06.024 DOI: https://doi.org/10.1016/j.jaci.2020.06.024
Tauber M, Balica S, Hsu CY, Jean-Decoster C, Lauze C, Redoules D, et al. Staphylococcus aureus density on lesional and nonlesional skin is strongly associated with disease severity in atopic dermatitis. J Allergy Clin Immunol 2016; 137: 1272-1274 e1273.
https://doi.org/10.1016/j.jaci.2015.07.052 DOI: https://doi.org/10.1016/j.jaci.2015.07.052
de Jongh GJ, Zeeuwen PL, Kucharekova M, Pfundt R, van der Valk PG, Blokx W, et al. High expression levels of keratinocyte antimicrobial proteins in psoriasis compared with atopic dermatitis. J Invest Dermatol 2005; 125: 1163-1173.
https://doi.org/10.1111/j.0022-202X.2005.23935.x DOI: https://doi.org/10.1111/j.0022-202X.2005.23935.x
Ong PY, Ohtake T, Brandt C, Strickland I, Boguniewicz M, Ganz T, et al. Endogenous antimicrobial peptides and skin infections in atopic dermatitis. N Engl J Med 2002; 347: 1151-1160.
https://doi.org/10.1056/NEJMoa021481 DOI: https://doi.org/10.1056/NEJMoa021481
Noore J, Noore A, Li B. Cationic antimicrobial peptide LL-37 is effective against both extra- and intracellular Staphylococcus aureus. Antimicrob Agents Chemother 2013; 57: 1283-1290.
https://doi.org/10.1128/AAC.01650-12 DOI: https://doi.org/10.1128/AAC.01650-12
Kang J, Dietz MJ, Li B. Antimicrobial peptide LL-37 is bactericidal against Staphylococcus aureus biofilms. PLoS One 2019; 14: e0216676.
https://doi.org/10.1371/journal.pone.0216676 DOI: https://doi.org/10.1371/journal.pone.0216676
Midorikawa K, Ouhara K, Komatsuzawa H, Kawai T, Yamada S, Fujiwara T, et al. Staphylococcus aureus susceptibility to innate antimicrobial peptides, beta-defensins and CAP18, expressed by human keratinocytes. Infect Immun 2003; 71: 3730-3739.
https://doi.org/10.1128/IAI.71.7.3730-3739.2003 DOI: https://doi.org/10.1128/IAI.71.7.3730-3739.2003
Howell MD, Gallo RL, Boguniewicz M, Jones JF, Wong C, Streib JE, et al. Cytokine milieu of atopic dermatitis skin subverts the innate immune response to vaccinia virus. Immunity 2006; 24: 341-348.
https://doi.org/10.1016/j.immuni.2006.02.006 DOI: https://doi.org/10.1016/j.immuni.2006.02.006
Gambichler T, Skrygan M, Tomi NS, Altmeyer P, Kreuter A. Changes of antimicrobial peptide mRNA expression in atopic eczema following phototherapy. Br J Dermatol 2006; 155: 1275-1278.
https://doi.org/10.1111/j.1365-2133.2006.07481.x DOI: https://doi.org/10.1111/j.1365-2133.2006.07481.x
Gambichler T, Skrygan M, Tomi NS, Othlinghaus N, Brockmeyer NH, Altmeyer P, et al. Differential mRNA expression of antimicrobial peptides and proteins in atopic dermatitis as compared to psoriasis vulgaris and healthy skin. Int Arch Allergy Immunol 2008; 147: 17-24.
https://doi.org/10.1159/000128582 DOI: https://doi.org/10.1159/000128582
Nomura I, Gao B, Boguniewicz M, Darst MA, Travers JB, Leung DY. Distinct patterns of gene expression in the skin lesions of atopic dermatitis and psoriasis: a gene microarray analysis. J Allergy Clin Immunol 2003; 112: 1195-1202.
https://doi.org/10.1016/j.jaci.2003.08.049 DOI: https://doi.org/10.1016/j.jaci.2003.08.049
Hata TR, Kotol P, Boguniewicz M, Taylor P, Paik A, Jackson M, et al. History of eczema herpeticum is associated with the inability to induce human beta-defensin (HBD)-2, HBD-3 and cathelicidin in the skin of patients with atopic dermatitis. Br J Dermatol 2010; 163: 659-661.
https://doi.org/10.1111/j.1365-2133.2010.09892.x DOI: https://doi.org/10.1111/j.1365-2133.2010.09892.x
He H, Bissonnette R, Wu J, Diaz A, Saint-Cyr Proulx E, Maari C, et al. Tape strips detect distinct immune and barrier profiles in atopic dermatitis and psoriasis. J Allergy Clin Immunol 2021; 147: 199-212.
https://doi.org/10.1016/j.jaci.2020.05.048 DOI: https://doi.org/10.1016/j.jaci.2020.05.048
Guttman-Yassky E, Diaz A, Pavel AB, Fernandes M, Lefferdink R, Erickson T, et al. Use of tape strips to detect immune and barrier abnormalities in the skin of children with early-onset atopic dermatitis. JAMA Dermatol 2019; 155: 1358-1370.
https://doi.org/10.1001/jamadermatol.2019.2983 DOI: https://doi.org/10.1001/jamadermatol.2019.2983
Harder J, Dressel S, Wittersheim M, Cordes J, Meyer-Hoffert U, Mrowietz U, et al. Enhanced expression and secretion of antimicrobial peptides in atopic dermatitis and after superficial skin injury. J Invest Dermatol 2010; 130: 1355-1364.
https://doi.org/10.1038/jid.2009.432 DOI: https://doi.org/10.1038/jid.2009.432
Asano S, Ichikawa Y, Kumagai T, Kawashima M, Imokawa G. Microanalysis of an antimicrobial peptide, beta-defensin-2, in the stratum corneum from patients with atopic dermatitis. Br J Dermatol 2008; 159: 97-104.
https://doi.org/10.1111/j.1365-2133.2008.08613.x DOI: https://doi.org/10.1111/j.1365-2133.2008.08613.x
Clausen ML, Jungersted JM, Andersen PS, Slotved HC, Krogfelt KA, Agner T. Human beta-defensin-2 as a marker for disease severity and skin barrier properties in atopic dermatitis. Br J Dermatol 2013; 169: 587-593.
https://doi.org/10.1111/bjd.12419 DOI: https://doi.org/10.1111/bjd.12419
Clausen ML, Slotved HC, Krogfelt KA, Agner T. Measurements of AMPs in stratum corneum of atopic dermatitis and healthy skin-tape stripping technique. Sci Rep 2018; 8: 1666.
https://doi.org/10.1038/s41598-018-20204-8 DOI: https://doi.org/10.1038/s41598-018-20204-8
Goo J, Ji JH, Jeon H, Kim MJ, Jeon SY, Cho MY, et al. Expression of antimicrobial peptides such as LL-37 and hBD-2 in nonlesional skin of atopic individuals. Pediatr Dermatol 2010; 27: 341-348.
https://doi.org/10.1111/j.1525-1470.2010.01122.x DOI: https://doi.org/10.1111/j.1525-1470.2010.01122.x
Guttman-Yassky E, Lowes MA, Fuentes-Duculan J, Zaba LC, Cardinale I, Nograles KE, et al. Low expression of the IL-23/Th17 pathway in atopic dermatitis compared to psoriasis. J Immunol 2008; 181: 7420-7427.
https://doi.org/10.4049/jimmunol.181.10.7420 DOI: https://doi.org/10.4049/jimmunol.181.10.7420
Howell MD, Novak N, Bieber T, Pastore S, Girolomoni G, Boguniewicz M, et al. Interleukin-10 downregulates anti-microbial peptide expression in atopic dermatitis. J Invest Dermatol 2005; 125: 738-745.
https://doi.org/10.1111/j.0022-202X.2005.23776.x DOI: https://doi.org/10.1111/j.0022-202X.2005.23776.x
Nomura I, Goleva E, Howell MD, Hamid QA, Ong PY, Hall CF, et al. Cytokine milieu of atopic dermatitis, as compared to psoriasis, skin prevents induction of innate immune response genes. J Immunol 2003; 171: 3262-3269.
https://doi.org/10.4049/jimmunol.171.6.3262 DOI: https://doi.org/10.4049/jimmunol.171.6.3262
Ballardini N, Johansson C, Lilja G, Lindh M, Linde Y, Scheynius A, et al. Enhanced expression of the antimicrobial peptide LL-37 in lesional skin of adults with atopic eczema. Br J Dermatol 2009; 161: 40-47.
https://doi.org/10.1111/j.1365-2133.2009.09095.x DOI: https://doi.org/10.1111/j.1365-2133.2009.09095.x
Mallbris L, Carlen L, Wei T, Heilborn J, Nilsson MF, Granath F, et al. Injury downregulates the expression of the human cathelicidin protein hCAP18/LL-37 in atopic dermatitis. Exp Dermatol 2010; 19: 442-449.
https://doi.org/10.1111/j.1600-0625.2009.00918.x DOI: https://doi.org/10.1111/j.1600-0625.2009.00918.x
Glaser R, Meyer-Hoffert U, Harder J. [Antimicrobial peptides in atopic dermatitis. A paradigm shift?]. Hautarzt 2009; 60: 761-762.
https://doi.org/10.1007/s00105-009-1836-8 DOI: https://doi.org/10.1007/s00105-009-1836-8
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Hungarian Scientific Research Fund
Grant numbers NKFIH K-128250;NKFIH K-142348;NKFIH PD-131689
