Protecting the boundary: The sentinel role of host defense peptides in the skin

Cellular and Molecular Life Sciences

Volumn 68, Issue 13, 2011, Pages 2189-2199

  Bernard, Jamie J ^a   Gallo, Richard L ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Antimicrobial peptides; Cathelicidin; Defensin; Innate immunity; Keratinocytes; Skin diseases

Indexed keywords

BETA DEFENSIN; CATHELICIDIN; CATHELICIDIN ANTIMICROBIAL PEPTIDE LL 37; CATHELICIDIN RELATED ANTIMICROBIAL PEPTIDE; DEFENSIN; POLYPEPTIDE ANTIBIOTIC AGENT; UNCLASSIFIED DRUG;

ACNE VULGARIS; ADAPTIVE IMMUNITY; ANGIOGENESIS; ANTIBACTERIAL ACTIVITY; ANTIFUNGAL ACTIVITY; ANTIVIRAL ACTIVITY; ATOPIC DERMATITIS; CELL DIFFERENTIATION; CELL MIGRATION; CELL PROLIFERATION; CYTOKINE PRODUCTION; DRUG STRUCTURE; HOST RESISTANCE; HUMAN; IMMUNOPATHOGENESIS; INNATE IMMUNITY; NONHUMAN; PEPTIDE ANALYSIS; PERMEABILITY BARRIER; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; PSORIASIS; REVIEW; ROSACEA; SKIN FUNCTION; SKIN INFECTION; SKIN PROTECTION; WOUND HEALING;

ANTIMICROBIAL CATIONIC PEPTIDES; HOST-PATHOGEN INTERACTIONS; HUMANS; SKIN; SKIN DISEASES, BACTERIAL;

MAMMALIA;

EID: 79960931881     PISSN: 1420682X     EISSN: 14209071     Source Type: Journal    
DOI: 10.1007/s00018-011-0712-8     Document Type: Review

References (134)

1. Cork MJ, Danby SG, Vasilopoulos Y, Hadgraft J, Lane ME, Moustafa M, Guy RH, Macgowan AL, Tazi-Ahnini R, Ward SJ (2009) Epidermal barrier dysfunction in atopic dermatitis. J Invest Dermatol 129:1892-1908
2. Proksch E, Brandner JM, Jensen JM (2008) The skin: an indispensable barrier. Exp Dermatol 17:1063-1072
3. Janeway CA Jr, Medzhitov R (2002) Innate immune recognition. Annu Rev Immunol 20:197-216
4. Zasloff M (2002) Antimicrobial peptides of multicellular organisms. Nature 415:389-395
5. Gallo RL, Huttner KM (1998) Antimicrobial peptides: an emerging concept in cutaneous biology. J Invest Dermatol 111:739-743 (Pubitemid 28509311)
6. Aberg KM, Man MQ, Gallo RL, Ganz T, Crumrine D, Brown BE, Choi EH, Kim DK, Schroder JM, Feingold KR, Elias PM (2008) Co-regulation and interdependence of the mammalian epidermal permeability and antimicrobial barriers. J Invest Dermatol 128:917-925 (Pubitemid 351374295)
7. Dorschner RA, Lin KH, Murakami M, Gallo RL (2003) Neonatal skin in mice and humans expresses increased levels of antimicrobial peptides: innate immunity during development of the adaptive response. Pediatr Res 53:566-572 (Pubitemid 36406725)
8. Frohm M, Agerberth B, Ahangari G, Stahle-Backdahl M, Liden S, Wigzell H, Gudmundsson GH (1997) The expression of the gene coding for the antibacterial peptide LL-37 is induced in human keratinocytes during inflammatory disorders. J Biol Chem 272:15258-15263 (Pubitemid 27255544)
9. Brahmachary M, Krishnan SP, Koh JL, Khan AM, Seah SH, Tan TW, Brusic V, Bajic VB (2004) ANTIMIC: a database of antimicrobial sequences. Nucleic Acids Res 32:D586-D589 (Pubitemid 38081726)
10. Fjell CD, Hancock RE, Cherkasov A (2007) AMPer: a database and an automated discovery tool for antimicrobial peptides. Bioinformatics 23:1148-1155 (Pubitemid 47050567)
11. Wang G, Li X, Wang Z (2009) APD2: the updated antimicrobial peptide database and its application in peptide design. Nucleic Acids Res 37:D933-D937
12. Jenssen H, Hamill P, Hancock RE (2006) Peptide antimicrobial agents. Clin Microbiol Rev 19:491-511 (Pubitemid 44137212)
13. Yeaman MR, Yount NY (2003) Mechanisms of antimicrobial peptide action and resistance. Pharmacol Rev 55:27-55 (Pubitemid 36268398)
14. Hancock RE, Lehrer R (1998) Cationic peptides: a new source of antibiotics. Trends Biotechnol 16:82-88 (Pubitemid 28055477)
15. Gennaro R, Zanetti M (2000) Structural features and biological activities of the cathelicidin-derived antimicrobial peptides. Biopolymers 55:31-49
16. Durr UH, Sudheendra US, Ramamoorthy A (2006) LL-37, the only human member of the cathelicidin family of antimicrobial peptides. Biochim Biophys Acta 1758:1408-1425 (Pubitemid 44436081)
17. Zanetti M (2004) Cathelicidins, multifunctional peptides of the innate immunity. J Leukoc Biol 75:39-48
18. Yamasaki K, Schauber J, Coda A, Lin H, Dorschner RA, Schechter NM, Bonnart C, Descargues P, Hovnanian A, Gallo RL (2006) Kallikrein-mediated proteolysis regulates the antimicrobial effects of cathelicidins in skin. FASEB J 20:2068-2080 (Pubitemid 44953906)
19. Murakami M, Lopez-Garcia B, Braff M, Dorschner RA, Gallo RL (2004) Postsecretory processing generates multiple cathelicidins for enhanced topical antimicrobial defense. J Immunol 172:3070-3077 (Pubitemid 38263696)
20. Wang TT, Nestel FP, Bourdeau V, Nagai Y, Wang Q, Liao J, Tavera-Mendoza L, Lin R, Hanrahan JW, Mader S, White JH (2004) Cutting edge: 1,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. J Immunol 173:2909-2912 (Pubitemid 39141992)
21. Liu PT, Stenger S, Li H, Wenzel L, Tan BH, Krutzik SR, Ochoa MT, Schauber J, Wu K, Meinken C, Kamen DL, Wagner M, Bals R, Steinmeyer A, Zugel U, Gallo RL, Eisenberg D, Hewison M, Hollis BW, Adams JS, Bloom BR, Modlin RL (2006) Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science 311:1770-1773
22. Schauber J, Dorschner RA, Coda AB, Buchau AS, Liu PT, Kiken D, Helfrich YR, Kang S, Elalieh HZ, Steinmeyer A, Zugel U, Bikle DD, Modlin RL, Gallo RL (2007) Injury enhances TLR2 function and antimicrobial peptide expression through a vitamin D-dependent mechanism. J Clin Invest 117:803-811 (Pubitemid 46348539)
23. Schauber J, Dorschner RA, Yamasaki K, Brouha B, Gallo RL (2006) Control of the innate epithelial antimicrobial response is cell-type specific and dependent on relevant microenvironmental stimuli. Immunology 118:509-519 (Pubitemid 44079569)
24. Gallo RL, Kim KJ, Bernfield M, Kozak CA, Zanetti M, Merluzzi L, Gennaro R (1997) Identification of CRAMP, a cathelin-related antimicrobial peptide expressed in the embryonic and adult mouse. J Biol Chem 272:13088-13093 (Pubitemid 27216731)
25. Peyssonaux C, Johnson RS (2004) An unexpected role for hypoxic response: oxygenation and inflammation. Cell Cycle 3:168-171
26. Peyssonnaux C, Boutin AT, Zinkernagel AS, Datta V, Nizet V, Johnson RS (2008) Critical role of HIF-1alpha in keratinocyte defense against bacterial infection. J Invest Dermatol 128:1964-1968 (Pubitemid 352001211)
27. Ganz T, Selsted ME, Szklarek D, Harwig SS, Daher K, Bainton DF, Lehrer RI (1985) Defensins. Natural peptide antibiotics of human neutrophils. J Clin Invest 76:1427-1435 (Pubitemid 16193690)
28. Selsted ME, Harwig SS, Ganz T, Schilling JW, Lehrer RI (1985) Primary structures of three human neutrophil defensins. J Clin Invest 76:1436-1439 (Pubitemid 16193691)
29. Koczulla AR, Bals R (2003) Antimicrobial peptides: current status and therapeutic potential. Drugs 63:389-406 (Pubitemid 36259526)
30. Selsted ME, Szklarek D, Ganz T, Lehrer RI (1985) Activity of rabbit leukocyte peptides against Candida albicans. Infect Immun 49:202-206 (Pubitemid 15062889)
31. Selsted ME, Szklarek D, Lehrer RI (1984) Purification and antibacterial activity of antimicrobial peptides of rabbit granulocytes. Infect Immun 45:150-154 (Pubitemid 14078932)
32. Daher KA, Selsted ME, Lehrer RI (1986) Direct inactivation of viruses by human granulocyte defensins. J Virol 60:1068-1074 (Pubitemid 17179284)
33. Nomura I, Goleva E, Howell MD, Hamid QA, Ong PY, Hall CF, Darst MA, Gao B, Boguniewicz M, Travers JB, Leung DY (2003) Cytokine milieu of atopic dermatitis, as compared to psoriasis, skin prevents induction of innate immune response genes. J Immunol 171:3262-3269 (Pubitemid 37093553)
34. Harder J, Bartels J, Christophers E, Schroder JM (1997) A peptide antibiotic from human skin. Nature 387:861
35. Lai Y, Cogen AL, Radek KA, Park HJ, Macleod DT, Leichtle A, Ryan AF, Di Nardo A, Gallo RL (2010) Activation of TLR2 by a small molecule produced by Staphylococcus epidermidis Increases antimicrobial defense against bacterial skin infections. J Invest Dermatol 130:2211-2221
36. Domachowske JB, Dyer KD, Adams AG, Leto TL, Rosenberg HF (1998) Eosinophil cationic protein/RNase 3 is another RNase A-family ribonuclease with direct antiviral activity. Nucleic Acids Res 26:3358-3363 (Pubitemid 28321399)
37. Harder J, Schroder JM (2002) RNase 7, a novel innate immune defense antimicrobial protein of healthy human skin. J Biol Chem 277:46779-46784 (Pubitemid 35417681)
38. Glaser R, Harder J, Lange H, Bartels J, Christophers E, Schroder JM (2005) Antimicrobial psoriasin (S100A7) protects human skin from Escherichia coli infection. Nat Immunol 6:57-64 (Pubitemid 40136696)
39. Radek KA, Lopez-Garcia B, Hupe M, Niesman IR, Elias PM, Taupenot L, Mahata SK, O'Connor DT, Gallo RL (2008) The neuroendocrine peptide catestatin is a cutaneous antimicrobial and induced in the skin after injury. J Invest Dermatol 128:1525-1534 (Pubitemid 351693209)
40. Weitzman I, Summerbell RC (1995) The dermatophytes. Clin Microbiol Rev 8:240-259
41. Wakabayashi H, Uchida K, Yamauchi K, Teraguchi S, Hayasawa H, Yamaguchi H (2000) Lactoferrin given in food facilitates dermatophytosis cure in guinea pig models. J Antimicrob Chemother 46:595-602
42. Franzke CW, Baici A, Bartels J, Christophers E, Wiedow O (1996) Antileukoprotease inhibits stratum corneum chymotryptic enzyme. Evidence for a regulative function in desquamation. J Biol Chem 271:21886-21890 (Pubitemid 26303810)
43. Wiedow O, Harder J, Bartels J, Streit V, Christophers E (1998) Antileukoprotease in human skin: an antibiotic peptide constitutively produced by keratinocytes. Biochem Biophys Res Commun 248:904-909 (Pubitemid 28404520)
44. Ashcroft GS, Lei K, Jin W, Longenecker G, Kulkarni AB, Greenwell-Wild T, Hale-Donze H, McGrady G, Song XY, Wahl SM (2000) Secretory leukocyte protease inhibitor mediates non-redundant functions necessary for normal wound healing. Nat Med 6:1147-1153
45. Lee DY, Huang CM, Nakatsuji T, Thiboutot D, Kang SA, Monestier M, Gallo RL (2009) Histone H4 is a major component of the antimicrobial action of human sebocytes. J Invest Dermatol 129:2489-2496
46. Schittek B, Hipfel R, Sauer B, Bauer J, Kalbacher H, Stevanovic S, Schirle M, Schroeder K, Blin N, Meier F, Rassner G, Garbe C (2001) Dermcidin: a novel human antibiotic peptide secreted by sweat glands. Nat Immunol 2:1133-1137 (Pubitemid 33130147)
47. Flad T, Bogumil R, Tolson J, Schittek B, Garbe C, Deeg M, Mueller CA, Kalbacher H (2002) Detection of dermcidin-derived peptides in sweat by ProteinChip technology. J Immunol Methods 270:53-62
48. Cogen AL, Yamasaki K, Sanchez KM, Dorschner RA, Lai Y, MacLeod DT, Torpey JW, Otto M, Nizet V, Kim JE, Gallo RL (2010) Selective antimicrobial action is provided by phenol-soluble modulins derived from Staphylococcus epidermidis, a normal resident of the skin. J Invest Dermatol 130:192-200
49. Nizet V, Ohtake T, Lauth X, Trowbridge J, Rudisill J, Dorschner RA, Pestonjamasp V, Piraino J, Huttner K, Gallo RL (2001) Innate antimicrobial peptide protects the skin from invasive bacterial infection. Nature 414:454-457 (Pubitemid 34173727)
50. Bals R, Weiner DJ, Moscioni AD, Meegalla RL, Wilson JM (1999) Augmentation of innate host defense by expression of a cathelicidin antimicrobial peptide. Infect Immun 67:6084-6089 (Pubitemid 29508140)
51. Morrison G, Kilanowski F, Davidson D, Dorin J (2002) Characterization of the mouse beta defensin 1, Defb1, mutant mouse model. Infect Immun 70:3053-3060 (Pubitemid 34564166)
52. Garcia JR, Jaumann F, Schulz S, Krause A, Rodriguez-Jimenez J, Forssmann U, Adermann K, Kluver E, Vogelmeier C, Becker D, Hedrich R, Forssmann WG, Bals R (2001) Identification of a novel, multifunctional beta-defensin (human beta-defensin 3) with specific antimicrobial activity. Its interaction with plasma membranes of Xenopus oocytes and the induction of macrophage chemoattraction. Cell Tissue Res 306:257-264
53. Menzies BE, Kenoyer A (2006) Signal transduction and nuclear responses in Staphylococcus aureus-induced expression of human beta-defensin 3 in skin keratinocytes. Infect Immun 74:6847-6854 (Pubitemid 44913160)
54. Bowdish DM, Davidson DJ, Lau YE, Lee K, Scott MG, Hancock RE (2005) Impact of LL-37 on anti-infective immunity. J Leukoc Biol 77:451-459 (Pubitemid 40489520)
55. Gallo RL, Murakami M, Ohtake T, Zaiou M (2002) Biology and clinical relevance of naturally occurring antimicrobial peptides. J Allergy Clin Immunol 110:823-831
56. Niyonsaba F, Iwabuchi K, Matsuda H, Ogawa H, Nagaoka I (2002) Epithelial cell-derived human beta-defensin-2 acts as a chemotaxin for mast cells through a pertussis toxin-sensitive and phospholipase C-dependent pathway. Int Immunol 14:421-426 (Pubitemid 34257769)
57. Niyonsaba F, Ogawa H, Nagaoka I (2004) Human beta-defensin-2 functions as a chemotactic agent for tumour necrosis factor-alpha-treated human neutrophils. Immunology 111:273-281 (Pubitemid 38365749)
58. Yang D, Chertov O, Bykovskaia SN, Chen Q, Buffo MJ, Shogan J, Anderson M, Schroder JM, Wang JM, Howard OM, Oppenheim JJ (1999) Beta-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6. Science 286:525-528
59. Soruri A, Grigat J, Forssmann U, Riggert J, Zwirner J (2007) beta-Defensins chemoattract macrophages and mast cells but not lymphocytes and dendritic cells: CCR6 is not involved. Eur J Immunol 37:2474-2486 (Pubitemid 47423617)
60. Niyonsaba F, Ushio H, Nagaoka I, Okumura K, Ogawa H (2005) The human beta-defensins (-1, -2, -3, -4) and cathelicidin LL-37 induce IL-18 secretion through p38 and ERK MAPK activation in primary human keratinocytes. J Immunol 175:1776-1784 (Pubitemid 41023082)
61. Niyonsaba F, Ushio H, Nakano N, Ng W, Sayama K, Hashimoto K, Nagaoka I, Okumura K, Ogawa H (2007) Antimicrobial peptides human beta-defensins stimulate epidermal keratinocyte migration, proliferation and production of proinflammatory cytokines and chemokines. J Invest Dermatol 127:594-604
62. Biragyn A, Ruffini PA, Leifer CA, Klyushnenkova E, Shakhov A, Chertov O, Shirakawa AK, Farber JM, Segal DM, Oppenheim JJ, Kwak LW (2002) Toll-like receptor 4-dependent activation of dendritic cells by beta-defensin 2. Science 298:1025-1029 (Pubitemid 35247310)
63. De Y, Chen Q, Schmidt AP, Anderson GM, Wang JM, Wooters J, Oppenheim JJ, Chertov O (2000) LL-37, the neutrophil granule- and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells. J Exp Med 192:1069-1074
64. Kurosaka K, Chen Q, Yarovinsky F, Oppenheim JJ, Yang D (2005) Mouse cathelin-related antimicrobial peptide chemoattracts leukocytes using formyl peptide receptor-like 1/mouse formyl peptide receptor-like 2 as the receptor and acts as an immune adjuvant. J Immunol 174:6257-6265 (Pubitemid 40663818)
65. Di Nardo A, Vitiello A, Gallo RL (2003) Cutting edge: mast cell antimicrobial activity is mediated by expression of cathelicidin antimicrobial peptide. J Immunol 170:2274-2278 (Pubitemid 36245611)
66. Davidson DJ, Currie AJ, Reid GS, Bowdish DM, MacDonald KL, Ma RC, Hancock RE, Speert DP (2004) The cationic antimicrobial peptide LL-37 modulates dendritic cell differentiation and dendritic cell-induced T cell polarization. J Immunol 172:1146-1156 (Pubitemid 38113775)
67. Zheng Y, Niyonsaba F, Ushio H, Nagaoka I, Ikeda S, Okumura K, Ogawa H (2007) Cathelicidin LL-37 induces the generation of reactive oxygen species and release of human alpha-defensins from neutrophils. Br J Dermatol 157:1124-1131 (Pubitemid 350115677)
68. Niyonsaba F, Iwabuchi K, Someya A, Hirata M, Matsuda H, Ogawa H, Nagaoka I (2002) A cathelicidin family of human antibacterial peptide LL-37 induces mast cell chemotaxis. Immunology 106:20-26 (Pubitemid 34437873)
69. Kandler K, Shaykhiev R, Kleemann P, Klescz F, Lohoff M, Vogelmeier C, Bals R (2006) The anti-microbial peptide LL-37 inhibits the activation of dendritic cells by TLR ligands. Int Immunol 18:1729-1736 (Pubitemid 44884035)
70. Mookherjee N, Brown KL, Bowdish DM, Doria S, Falsafi R, Hokamp K, Roche FM, Mu R, Doho GH, Pistolic J, Powers JP, Bryan J, Brinkman FS, Hancock RE (2006) Modulation of the TLR-mediated inflammatory response by the endogenous human host defense peptide LL-37. J Immunol 176:2455-2464 (Pubitemid 43201696)
71. Mookherjee N, Wilson HL, Doria S, Popowych Y, Falsafi R, Yu JJ, Li Y, Veatch S, Roche FM, Brown KL, Brinkman FS, Hokamp K, Potter A, Babiuk LA, Griebel PJ, Hancock RE (2006) Bovine and human cathelicidin cationic host defense peptides similarly suppress transcriptional responses to bacterial lipopolysaccharide. J Leukoc Biol 80:1563-1574 (Pubitemid 44904995)
72. Di Nardo A, Braff MH, Taylor KR, Na C, Granstein RD, McInturff JE, Krutzik S, Modlin RL, Gallo RL (2007) Cathelicidin antimicrobial peptides block dendritic cell TLR4 activation and allergic contact sensitization. J Immunol 178:1829-1834 (Pubitemid 46154655)
73. Morioka Y, Yamasaki K, Leung D, Gallo RL (2008) Cathelicidin antimicrobial peptides inhibit hyaluronan-induced cytokine release and modulate chronic allergic dermatitis. J Immunol 181:3915-3922
74. Ong PY, Ohtake T, Brandt C, Strickland I, Boguniewicz M, Ganz T, Gallo RL, Leung DY (2002) Endogenous antimicrobial peptides and skin infections in atopic dermatitis. N Engl J Med 347:1151-1160
75. Rieg S, Steffen H, Seeber S, Humeny A, Kalbacher H, Dietz K, Garbe C, Schittek B (2005) Deficiency of dermcidin-derived antimicrobial peptides in sweat of patients with atopic dermatitis correlates with an impaired innate defense of human skin in vivo. J Immunol 174:8003-8010 (Pubitemid 40806311)
76. Leung DY (2003) Infection in atopic dermatitis. Curr Opin Pediatr 15:399-404
77. Machura E, Mazur B, Golemiec E, Pindel M, Halkiewicz F (2008) Staphylococcus aureus skin colonization in atopic dermatitis children is associated with decreased IFN-gamma production by peripheral blood CD4+ and CD8+ T cells. Pediatr Allergy Immunol 19:37-45
78. Howell MD, Gallo RL, Boguniewicz M, Jones JF, Wong C, Streib JE, Leung DY (2006) Cytokine milieu of atopic dermatitis skin subverts the innate immune response to vaccinia virus. Immunity 24:341-348
79. Howell MD, Wollenberg A, Gallo RL, Flaig M, Streib JE, Wong C, Pavicic T, Boguniewicz M, Leung DY (2006) Cathelicidin deficiency predisposes to eczema herpeticum. J Allergy Clin Immunol 117:836-841
80. Wollenberg A, Wetzel S, Burgdorf WH, Haas J (2003) Viral infections in atopic dermatitis: pathogenic aspects and clinical management. J Allergy Clin Immunol 112:667-674 (Pubitemid 37260380)
81. Howell MD, Novak N, Bieber T, Pastore S, Girolomoni G, Boguniewicz M, Streib J, Wong C, Gallo RL, Leung DY (2005) Interleukin-10 downregulates anti-microbial peptide expression in atopic dermatitis. J Invest Dermatol 125:738-745
82. Homey B, Steinhoff M, Ruzicka T, Leung DY (2006) Cytokines and chemokines orchestrate atopic skin inflammation. J Allergy Clin Immunol 118:178-189 (Pubitemid 43946487)
83. Howell MD, Boguniewicz M, Pastore S, Novak N, Bieber T, Girolomoni G, Leung DY (2006) Mechanism of HBD-3 deficiency in atopic dermatitis. Clin Immunol 121:332-338 (Pubitemid 44768007)
84. Kaburagi Y, Shimada Y, Nagaoka T, Hasegawa M, Takehara K, Sato S (2001) Enhanced production of CC-chemokines (RANTES, MCP-1, MIP-1alpha, MIP-1beta, and eotaxin) in patients with atopic dermatitis. Arch Dermatol Res 293:350-355 (Pubitemid 32757477)
85. Campbell JJ, Butcher EC (2000) Chemokines in tissue-specific and microenvironment-specific lymphocyte homing. Curr Opin Immunol 12:336-341 (Pubitemid 30240545)
86. Jeong CW, Ahn KS, Rho NK, Park YD, Lee DY, Lee JH, Lee ES, Yang JM (2003) Differential in vivo cytokine mRNA expression in lesional skin of intrinsic vs. extrinsic atopic dermatitis patients using semiquantitative RT-PCR. Clin Exp Allergy 33:1717-1724
87. Schwarz T (2008) 25 years of UV-induced immunosuppression mediated by T cells-from disregarded T suppressor cells to highly respected regulatory T cells. Photochem Photobiol 84:10-18
88. Lehmann B, Genehr T, Knuschke P, Pietzsch J, Meurer M (2001) UVB-induced conversion of 7-dehydrocholesterol to 1alpha, 25-dihydroxyvitamin D3 in an in vitro human skin equivalent model. J Invest Dermatol 117:1179-1185 (Pubitemid 34205915)
89. Mallbris L, Edstrom DW, Sundblad L, Granath F, Stahle M (2005) UVB upregulates the antimicrobial protein hCAP18 mRNA in human skin. J Invest Dermatol 125:1072-1074
90. Hata T (2010) History of eczema herpeticum is associated with the inability to induced HBD-2, HBD-3 and cathelicidin in the skin of patients with atopic dermatitis. Br J Dermatol 163:659-661
91. Nickoloff BJ, Nestle FO (2004) Recent insights into the immunopathogenesis of psoriasis provide new therapeutic opportunities. J Clin Invest 113:1664-1675 (Pubitemid 39071656)
92. Hollox EJ, Huffmeier U, Zeeuwen PL, Palla R, Lascorz J, Rodijk-Olthuis D, van de Kerkhof PC, Traupe H, de Jongh G, den Heijer M, Reis A, Armour JA, Schalkwijk J (2008) Psoriasis is associated with increased beta-defensin genomic copy number. Nat Genet 40:23-25
93. Huh WK, Oono T, Shirafuji Y, Akiyama H, Arata J, Sakaguchi M, Huh NH, Iwatsuki K (2002) Dynamic alteration of human beta-defensin 2 localization from cytoplasm to intercellular space in psoriatic skin. J Mol Med 80:678-684 (Pubitemid 35471733)
94. Harder J, Schroder JM (2005) Psoriatic scales: a promising source for the isolation of human skin-derived antimicrobial proteins. J Leukoc Biol 77:476-486 (Pubitemid 40489523)
95. Schauber J, Gallo RL (2009) Antimicrobial peptides and the skin immune defense system. J Allergy Clin Immunol 124:R13-R18
96. Lande R, Gregorio J, Facchinetti V, Chatterjee B, Wang YH, Homey B, Cao W, Wang YH, Su B, Nestle FO, Zal T, Mellman I, Schroder JM, Liu YJ, Gilliet M (2007) Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Nature 449:564-569 (Pubitemid 47525141)
97. Crawford GH, Pelle MT, James WD (2004) Rosacea: I. Etiology, pathogenesis, and subtype classification. J Am Acad Dermatol 51:327-341 (quiz 342-324)
98. 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 (2007) Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea. Nat Med 13:975-980 (Pubitemid 47222043)
99. Koczulla R, von Degenfeld G, Kupatt C, Krotz F, Zahler S, Gloe T, Issbrucker K, Unterberger P, Zaiou M, Lebherz C, Karl A, Raake P, Pfosser A, Boekstegers P, Welsch U, Hiemstra PS, Vogelmeier C, Gallo RL, Clauss M, Bals R (2003) An angiogenic role for the human peptide antibiotic LL-37/hCAP-18. J Clin Invest 111:1665-1672 (Pubitemid 38057748)
100. Jansen T, Krug S, Kind P, Plewig G, Messer G (2004) BsmI polymorphism of the vitamin D receptor gene in patients with the fulminant course of rosacea conglobata (Rosacea fulminans). J Dermatol 31:244-246 (Pubitemid 38478357)
101. Degitz K, Placzek M, Borelli C, Plewig G (2007) Pathophysiology of acne. J Dtsch Dermatol Ges 5:316-323
102. Toyoda M, Morohashi M (2001) Pathogenesis of acne. Med Electron Microsc 34:29-40
103. Philpott MP (2003) Defensins and acne. Mol Immunol 40:457-462
104. Oono T, Huh WK, Shirafuji Y, Akiyama H, Iwatsuki K (2003) Localization of human beta-defensin-2 and human neutrophil peptides in superficial folliculitis. Br J Dermatol 148:188-191 (Pubitemid 36114898)
105. Gambichler T, Skrygan M, Huyn J, Bechara FG, Sand M, Altmeyer P, Kreuter A (2006) Pattern of mRNA expression of beta-defensins in basal cell carcinoma. BMC Cancer 6:163
106. Dorschner RA, Pestonjamasp VK, Tamakuwala S, Ohtake T, Rudisill J, Nizet V, Agerberth B, Gudmundsson GH, Gallo RL (2001) Cutaneous injury induces the release of cathelicidin antimicrobial peptides active against group A Streptococcus. J Invest Dermatol 117:91-97 (Pubitemid 32652444)
107. Heilborn JD, Nilsson MF, Kratz G, Weber G, Sorensen O, Borregaard N, Stahle-Backdahl M (2003) The cathelicidin antimicrobial peptide LL-37 is involved in re-epithelialization of human skin wounds and is lacking in chronic ulcer epithelium. J Invest Dermatol 120:379-389 (Pubitemid 36298423)
108. Frohm M, Gunne H, Bergman AC, Agerberth B, Bergman T, Boman A, Liden S, Jornvall H, Boman HG (1996) Biochemical and antibacterial analysis of human wound and blister fluid. Eur J Biochem 237:86-92 (Pubitemid 26110276)
109. Baroni A, Donnarumma G, Paoletti I, Longanesi-Cattani I, Bifulco K, Tufano MA, Carriero MV (2009) Antimicrobial human beta-defensin-2 stimulates migration, proliferation and tube formation of human umbilical vein endothelial cells. Peptides 30:267-272
110. Gallo RL, Ono M, Povsic T, Page C, Eriksson E, Klagsbrun M, Bernfield M (1994) Syndecans, cell surface heparan sulfate proteoglycans, are induced by a proline-rich antimicrobial peptide from wounds. Proc Natl Acad Sci USA 91:11035-11039 (Pubitemid 24349620)
111. Tokumaru S, Sayama K, Shirakata Y, Komatsuzawa H, Ouhara K, Hanakawa Y, Yahata Y, Dai X, Tohyama M, Nagai H, Yang L, Higashiyama S, Yoshimura A, Sugai M, Hashimoto K (2005) Induction of keratinocyte migration via transactivation of the epidermal growth factor receptor by the antimicrobial peptide LL-37. J Immunol 175:4662-4668 (Pubitemid 41362007)
112. Yin J, Yu FS (2010) LL-37 promotes high glucose-attenuated epithelial wound healing via EGFR transactivation in organ cultured corneas. Invest Ophthalmol Vis Sci 51:1891-1897
113. Carretero M, Escamez MJ, Garcia M, Duarte B, Holguin A, Retamosa L, Jorcano JL, Rio MD, Larcher F (2008) In vitro and in vivo wound healing-promoting activities of human cathelicidin LL-37. J Invest Dermatol 128:223-236
114. Park HJ, Cho DH, Kim HJ, Lee JY, Cho BK, Bang SI, Song SY, Yamasaki K, Di Nardo A, Gallo RL (2009) Collagen synthesis is suppressed in dermal fibroblasts by the human antimicrobial peptide LL-37. J Invest Dermatol 129:843-850
115. Hirsch T, Spielmann M, Zuhaili B, Fossum M, Metzig M, Koehler T, Steinau HU, Yao F, Onderdonk AB, Steinstraesser L, Eriksson E (2009) Human beta-defensin-3 promotes wound healing in infected diabetic wounds. J Gene Med 11:220-228
116. Hancock RE, Sahl HG (2006) Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies. Nat Biotechnol 24:1551-1557 (Pubitemid 44967479)
117. Steinstraesser L, Kraneburg UM, Hirsch T, Kesting M, Steinau HU, Jacobsen F, Al-Benna S (2009) Host defense peptides as effector molecules of the innate immune response: a sledge-hammer for drug resistance? Int J Mol Sci 10:3951-3970
118. Liu L, Roberts AA, Ganz T (2003) By IL-1 signaling, monocyte-derived cells dramatically enhance the epidermal antimicrobial response to lipopolysaccharide. J Immunol 170:575-580 (Pubitemid 36026185)
119. Harder J, Bartels J, Christophers E, Schroder JM (2001) Isolation and characterization of human beta-defensin-3, a novel human inducible peptide antibiotic. J Biol Chem 276:5707-5713
120. Cumberbatch M, Dearman RJ, Uribe-Luna S, Headon DR, Ward PP, Conneely OM, Kimber I (2000) Regulation of epidermal Langerhans cell migration by lactoferrin. Immunology 100:21-28 (Pubitemid 30242878)
121. Marchini G, Lindow S, Brismar H, Stabi B, Berggren V, Ulfgren AK, Lonne-Rahm S, Agerberth B, Gudmundsson GH (2002) The newborn infant is protected by an innate antimicrobial barrier: peptide antibiotics are present in the skin and vernix caseosa. Br J Dermatol 147:1127-1134 (Pubitemid 36963018)
122. Wingens M, van Bergen BH, Hiemstra PS, Meis JF, van Vlijmen-Willems IM, Zeeuwen PL, Mulder J, Kramps HA, van Ruissen F, Schalkwijk J (1998) Induction of SLPI (ALP/HUSI-I) in epidermal keratinocytes. J Invest Dermatol 111:996-1002 (Pubitemid 29115165)
123. Simpson AJ, Maxwell AI, Govan JR, Haslett C, Sallenave JM (1999) Elafin (elastase-specific inhibitor) has anti-microbial activity against gram-positive and gram-negative respiratory pathogens. FEBS Lett 452:309-313 (Pubitemid 29301766)
124. Meyer-Hoffert U, Wichmann N, Schwichtenberg L, White PC, Wiedow O (2003) Supernatants of Pseudomonas aeruginosa induce the Pseudomonas-specific antibiotic elafin in human keratinocytes. Exp Dermatol 12:418-425 (Pubitemid 36992416)
125. Cutuli M, Cristiani S, Lipton JM, Catania A (2000) Antimicrobial effects of alpha-MSH peptides. J Leukoc Biol 67:233-239
126. Schauer E, Trautinger F, Kock A, Schwarz A, Bhardwaj R, Simon M, Ansel JC, Schwarz T, Luger TA (1994) Proopiomelanocortin-derived peptides are synthesized and released by human keratinocytes. J Clin Invest 93:2258-2262 (Pubitemid 24143110)
127. Ali RS, Falconer A, Ikram M, Bissett CE, Cerio R, Quinn AG (2001) Expression of the peptide antibiotics human beta defensin-1 and human beta defensin-2 in normal human skin. J Invest Dermatol 117:106-111 (Pubitemid 32652446)
128. Oono T, Matsuura H, Morizane S, Yamasaki O, Iwatsuki K (2006) A case of infectious eccrine hidradenitis. J Dermatol 33:142-145 (Pubitemid 43362928)
129. Chronnell CM, Ghali LR, Ali RS, Quinn AG, Holland DB, Bull JJ, Cunliffe WJ, McKay IA, Philpott MP, Muller-Rover S (2001) Human beta defensin-1 and -2 expression in human pilosebaceous units: upregulation in acne vulgaris lesions. J Invest Dermatol 117:1120-1125
130. Harwig SS, Ganz T, Lehrer RI (1994) Neutrophil defensins: purification, characterization, and antimicrobial testing. Methods Enzymol 236:160-172 (Pubitemid 24283612)
131. Caccavo D, Pellegrino NM, Altamura M, Rigon A, Amati L, Amoroso A, Jirillo E (2002) Antimicrobial and immunoregulatory functions of lactoferrin and its potential therapeutic application. J Endotoxin Res 8:403-417 (Pubitemid 36104594)
132. Belaaouaj A, Kim KS, Shapiro SD (2000) Degradation of outer membrane protein A in Escherichia coli killing by neutrophil elastase. Science 289:1185-1188
133. Tang YQ, Yeaman MR, Selsted ME (2002) Antimicrobial peptides from human platelets. Infect Immun 70:6524-6533 (Pubitemid 35387877)
134. Stenger S, Hanson DA, Teitelbaum R, Dewan P, Niazi KR, Froelich CJ, Ganz T, Thoma-Uszynski S, Melian A, Bogdan C, Porcelli SA, Bloom BR, Krensky AM, Modlin RL (1998) An antimicrobial activity of cytolytic T cells mediated by granulysin. Science 282:121-125 (Pubitemid 28471143)