Epithelial cell-derived antimicrobial peptides are multifunctional agents that bridge innate and adaptive immunity

Periodontology 2000

Volumn 54, Issue 1, 2010, Pages 195-206

  McCormick, Thomas S ^a   Weinberg, Aaron ^a  

^a NONE

Author keywords

[No Author keywords available]

Indexed keywords

ANTIMICROBIAL CATIONIC PEPTIDE; BETA DEFENSIN; LIPOPOLYSACCHARIDE;

ANIMAL; ARTICLE; EPITHELIUM CELL; HOST PATHOGEN INTERACTION; HUMAN; IMMUNOLOGY; IMMUNOMODULATION; METABOLISM; MOUTH TUMOR; MUCOSAL IMMUNITY; NEUTROPHIL CHEMOTAXIS; PHYSIOLOGY; VASCULARIZATION;

ANIMALS; ANTIMICROBIAL CATIONIC PEPTIDES; BETA-DEFENSINS; CHEMOTAXIS, LEUKOCYTE; EPITHELIAL CELLS; HOST-PATHOGEN INTERACTIONS; HUMANS; IMMUNITY, MUCOSAL; IMMUNOMODULATION; LIPOPOLYSACCHARIDES; MOUTH NEOPLASMS;

EID: 77955764021     PISSN: 09066713     EISSN: 16000757     Source Type: Journal    
DOI: 10.1111/j.1600-0757.2010.00373.x     Document Type: Article

References (104)

1. Aarbiou J, Ertmann M, van Wetering S, van Noort P, Rook D, Rabe KF, Litvinov SV, van Krieken JH, de Boer WI, Hiemstra PS. Human neutrophil defensins induce lung epithelial cell proliferation in vitro. J Leukoc Biol 2002, 1:167-174.
2. Aarbiou J, Verhoosel RM, Van Wetering S, De Boer WI, Van Krieken JH, Litvinov SV, Rabe KF, Hiemstra PS. Neutrophil defensins enhance lung epithelial wound closure and mucin gene expression in vitro. Am J Respir Cell Mol Biol 2004, 2:193-201.
3. Allaker RP, Zihni C, Kapas S. An investigation into the antimicrobial effects of adrenomedullin on members of the skin, oral, respiratory tract and gut microflora. FEMS Immunol Med Microbiol 1999, 4:289-293.
4. Bajaj-Elliott M, Fedeli P, Smith GV, Domizio P, Maher L, Ali RS, Quinn AG, Farthing MJ. Modulation of host antimicrobial peptide (beta-defensins 1 and 2) expression during gastritis. Gut 2002, 3:356-361.
5. Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature 1998, 6673:245-252.
6. Biragyn A, Ruffini PA, Leifer CC, Klyushnenkova E, Shakhov A, Chertov O, Shirakawa AK, Farber JM, Segal DM, Oppenheim FG, Kwak LW. Toll-like receptor 4-dependent activation of dendritic cells by beta-defensin 2. Science 2002, 298:1025-1029.
7. Biragyn A, Surenhu M, Yang D, Ruffini PA, Haines BA, Klyushnenkova E, Oppenheim JJ, Kwak LW. Mediators of innate immunity that target immature, but not mature, dendritic cells induce antitumor immunity when genetically fused with nonimmunogenic tumor antigens. J Immunol 2001, 11:6644-6653.
8. Boe R, Silvola J, Yang J, Moens U, McCray PB, Stenfors LE, Seljfelid R. Human beta-defensin-1 mRNA is transcribed in tympanic membrane and adjacent auditory canal epithelium. Infect Immun 1999, 9:4843-4846.
9. Bonass WA, High AS, Owen PJ, Devine DA. Expression of beta-defensin genes by human salivary glands. Oral Microbiol Immunol 1999, 6:371-374.
10. Borregaard N, Cowland JB. Neutrophil gelatinase-associated lipocalin, a siderophore-binding eukaryotic protein. Biometals 2006, 2:211-215.
11. Brogden KA, Heidari M, Sacco RE, Palmquist D, Guthmiller JM, Johnson GK, Jia HP, Tack BF, McCray PB. Defensin-induced adaptive immunity in mice and its potential in preventing periodontal disease. Oral Microbiol Immunol 2003, 2:95-99.
12. Carretero M, Escamez MJ, Garcia M, Duarte B, Holguin A, Retamosa L, Jorcano JL, Rio MD, Larcher F. In vitro and in vivo wound healing-promoting activities of human cathelicidin LL-37. J Invest Dermatol 2008, 1:223-236.
13. Caux C, Massacrier C, Vanbervliet B, Dubois B, Van Kooten C, Durand I, Banchereau J. Activation of human dendritic cells through CD40 cross-linking. J Exp Med 1994, 4:1263-1272.
14. Chen X, Niyonsaba F, Ushio H, Hara M, Yokoi H, Matsumoto K, Saito H, Nagaoka I, Ikeda S, Okumura K, Ogawa H. Antimicrobial peptides human beta-defensin (hBD)-3 and hBD-4 activate mast cells and increase skin vascular permeability. Eur J Immunol 2007, 2:434-444.
15. Chen X, Niyonsaba F, Ushio H, Nagaoka I, Ikeda S, Okumura K, Ogawa H. Human cathelicidin LL-37 increases vascular permeability in the skin via mast cell activation, and phosphorylates MAP kinases p38 and ERK in mast cells. J Dermatol Sci 2006, 1:63-66.
16. Chertov O, Michiel DF, Xu L, Wang JM, Tani K, Murphy WJ, Longo DL, Taub DD, Oppenheim JJ. Identification of defensin-1, defensin-2, and CAP37/azurocidin as T-cell chemoattractant proteins released from interleukin-8-stimulated neutrophils. J Biol Chem 1996, 6:2935-2940.
17. Clohessy PA, Golden BE. Calprotectin-mediated zinc chelation as a biostatic mechanism in host defence. Scand J Immunol 1995, 5:551-556.
18. Coffelt SB, Marini FC, Watson K, Zwezdaryk KJ, Dembinski JL, LaMarca HL, Tomchuck SL, Honer zu Bentrup K, Danka ES, Henkle SL, Scandurro AB. The pro-inflammatory peptide LL-37 promotes ovarian tumor progression through recruitment of multipotent mesenchymal stromal cells. Proc Natl Acad Sci U S A 2009, 10:3806-3811.
19. Coussens LM, Werb Z. Inflammation and cancer. Nature 2002, 6917:860-867.
20. Dale BA, Kimball JR, Krisanaprakornkit S, Roberts F, Robinovitch M, O'Neal R, Valore EV, Ganz T, Anderson GM, Weinberg A. Localized antimicrobial peptide expression in human gingiva. J Periodontal Res 2001, 5:285-294.
21. Davidson DJ, Currie AJ, Reid GS, Bowdish DM, MacDonald KL, Ma RC, Hancock RE, Speert DP. The cationic antimicrobial peptide LL-37 modulates dendritic cell differentiation and dendritic cell-induced T cell polarization. J Immunol 2004, 2:1146-1156.
22. De Y, Chen Q, Schmidt AP, Anderson GM, Wang JM, Wooters J, Oppenheim JJ, Chertov O. 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 2000, 7:1069-1074.
23. Diamond G, Zasloff M, Eck H, Brasseur M, Maloy WL, Bevins CL. Tracheal antimicrobial peptide, a cysteine-rich peptide from mammalian tracheal mucosa: peptide isolation and cloning of a cDNA. Proc Natl Acad Sci U S A 1991, 9:3952-3956.
24. Dunsche A, Acil Y, Dommisch H, Siebert R, Schroder JM, Jepsen S. The novel human beta-defensin-3 is widely expressed in oral tissues. Eur J Oral Sci 2002, 2:121-124.
25. Eckert RL, Broome AM, Ruse M, Robinson N, Ryan D, Lee K. S100 proteins in the epidermis. J Invest Dermatol 2004, 1:23-33.
26. Elssner A, Duncan M, Gavrilin M, Wewers MD. A novel P2X7 receptor activator, the human cathelicidin-derived peptide LL37, induces IL-1 beta processing and release. J Immunol 2004, 8:4987-4994.
27. Feng Z, Dubyak GR, Lederman MM, Weinberg A. Cutting edge: human beta defensin 3 - a novel antagonist of the HIV-1 coreceptor CXCR4. J Immunol 2006, 2:782-786.
28. Frohm M, Agerberth B, Ahangari G, Stahle-Backdahl M, Liden S, Wigzell H, Gudmundsson GH. The expression of the gene coding for the antibacterial peptide LL-37 is induced in human keratinocytes during inflammatory disorders. J Biol Chem 1997, 24:15258-15263.
29. Funderburg N, Lederman MM, Feng Z, Drage MG, Jadlowsky J, Harding CV, Weinberg A, Sieg SF. Human-defensin-3 activates professional antigen-presenting cells via Toll-like receptors 1 and 2. Proc Natl Acad Sci U S A 2007, 47:18631-18635.
30. 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. 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 2001, 2:257-264.
31. Glaser R, Harder J, Lange H, Bartels J, Christophers E, Schroder JM. Antimicrobial psoriasin (S100A7) protects human skin from Escherichia coli infection. Nat Immunol 2005, 1:57-64.
32. Goetz DH, Holmes MA, Borregaard N, Bluhm ME, Raymond KN, Strong RK. The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition. Mol Cell 2002, 5:1033-1043.
33. Gu L, Tseng S, Horner RM, Tam C, Loda M, Rollins BJ. Control of TH2 polarization by the chemokine monocyte chemoattractant protein-1. Nature 2000, 6776:407-411.
34. Hancock RE, Brown KL, Mookherjee N. Host defence peptides from invertebrates - emerging antimicrobial strategies. Immunobiology 2006, 4:315-322.
35. Harder J, Bartels J, Christophers E, Schroder JM. Isolation and characterization of human beta-defensin-3, a novel human inducible peptide antibiotic. J Biol Chem 2001, 8:5707-5713.
36. Harder J, Bartels J, Christophers E, Schroder JM. A peptide antibiotic from human skin. Nature 1997, 6636:861.
37. Harder J, Schroder JM. RNase 7, a novel innate immune defense antimicrobial protein of healthy human skin. J Biol Chem 2002, 48:46779-46784.
38. Haynes RJ, McElveen JE, Dua HS, Tighe PJ, Liversidge J. Expression of human beta-defensins in intraocular tissues. Invest Ophthalmol Vis Sci 2000, 10:3026-3031.
39. Heilborn JD, Nilsson MF, Kratz G, Weber G, Sorensen O, Borregaard N, Stahle-Backdahl M. The cathelicidin anti-microbial peptide LL-37 is involved in re-epithelialization of human skin wounds and is lacking in chronic ulcer epithelium. J Invest Dermatol 2003, 3:379-389.
40. Heizmann CW, Fritz G, Schafer BW. S100 proteins: structure, functions and pathology. Front Biosci 2002, 7:d1356-d1368.
41. Hiemstra PS, Maassen RJ, Stolk J, Heinzel-Wieland R, Steffens GJ, Dijkman JH. Antibacterial activity of antileukoprotease. Infect Immun 1996, 11:4520-4524.
42. Hodge JW, Rad AN, Grosenbach DW, Sabzevari H, Yafal AG, Gritz L, Schlom J. Enhanced activation of T cells by dendritic cells engineered to hyperexpress a triad of costimulatory molecules. J Natl Cancer Inst 2000, 15:1228-1239.
43. Imai T, Nagira M, Takagi S, Kakizaki M, Nishimura M, Wang J, Gray PW, Matsushima K, Yoshie O. Selective recruitment of CCR4-bearing Th2 cells toward antigen-presenting cells by the CC chemokines thymus and activation-regulated chemokine and macrophage-derived chemokine. Int Immunol 1999, 1:81-88.
44. Kang T, Yi J, Guo A, Wang X, Overall CM, Jiang W, Elde R, Borregaard N, Pei D. Subcellular distribution and cytokine- and chemokine-regulated secretion of leukolysin/MT6-MMP/MMP-25 in neutrophils. J Biol Chem 2001, 24:21960-21968.
45. Kapas S, Bansal A, Bhargava V, Maher R, Malli D, Hagi-Pavli E, Allaker RP. Adrenomedullin expression in pathogen-challenged oral epithelial cells. Peptides 2001, 9:1485-1489.
46. Karpus WJ, Lukacs NW, Kennedy KJ, Smith WS, Hurst SD, Barrett TA. Differential CC chemokine-induced enhancement of T helper cell cytokine production. J Immunol 1997, 9:4129-4136.
47. Kawsar HI, Weinberg A, Hirsch SA, Venizelos A, Howell S, Jiang B, Jin G. Overexpression of human beta-defensin-3 in oral dysplasia: potential role in macrophage trafficking. Oral Oncol 2009, 8:50-56.
48. Kazal LA, Spicer DS, Brahinsky RA. Isolation of a crystalline trypsin inhibitor-anticoagulant protein from pancreas. J Am Chem Soc 1948, 9:3034-3040.
49. Kjeldsen L, Bainton DF, Sengelov H, Borregaard N. Structural and functional heterogeneity among peroxidase-negative granules in human neutrophils: identification of a distinct gelatinase-containing granule subset by combined immunocytochemistry and subcellular fractionation. Blood 1993, 10:3183-3191.
50. 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. An angiogenic role for the human peptide antibiotic LL-37/hCAP-18. J Clin Invest 2003, 11:1665-1672.
51. Krisanaprakornkit S, Kimball JR, Weinberg A, Darveau RP, Bainbridge BW, Dale BA. Inducible expression of human beta-defensin 2 by Fusobacterium nucleatum in oral epithelial cells: multiple signaling pathways and role of commensal bacteria in innate immunity and the epithelial barrier. Infect Immun 2000, 5:2907-2915.
52. Krisanaprakornkit S, Weinberg A, Perez CN, Dale BA. Expression of the peptide antibiotic human beta-defensin 1 in cultured gingival epithelial cells and gingival tissue. Infect Immun 1998, 9:4222-4228.
53. Lillard JW, Boyaka PN, Chertov O, Oppenheim JJ, McGhee JR. Mechanisms for induction of acquired host immunity by neutrophil peptide defensins. Proc Natl Acad Sci U S A 1999, 2:651-656.
54. Liu L, Wang L, Jia HP, Zhao C, Heng HHQ, Schutte BC, McCray PB, Ganz T. Structure and mapping of the human beta-defensin HBD-2 gene and its expression at sites of inflammation. Gene 1998, 2:237-244.
55. Madsen P, Rasmussen HH, Leffers H, Honore B, Dejgaard K, Olsen E, Kiil J, Walbum E, Andersen AH, Basse B, Lauridsen JB, Ratz GP, Celis A, Vandekerckhove J, Celis JE. Molecular cloning, occurrence, and expression of a novel partially secreted protein " psoriasin" that is highly up-regulated in psoriatic skin. J Invest Dermatol 1991, 4:701-712.
56. Mathews M, Jia HP, Guthmiller JM, Losh G, Graham S, Johnson GK, Tack BF, McCray PB. Production of beta-defensin antimicrobial peptides by the oral mucosa and salivary glands. Infect Immun 1999, 6:2740-2745.
57. McCray PB, Bentley L. Human airway epithelia express a beta-defensin. Am J Respir Cell Mol Biol 1997, 3:343-349.
58. Nagaoka I, Hirota S, Niyonsaba F, Hirata M, Adachi Y, Tamura H, Heumann D. Cathelicidin family of antibacterial peptides CAP18 and CAP11 inhibit the expression of TNF-alpha by blocking the binding of LPS to CD14(+) cells. J Immunol 2001, 6:3329-3338.
59. Nagaoka I, Tamura H, Hirata M. An antimicrobial cathelicidin peptide, human CAP18/LL-37, suppresses neutrophil apoptosis via the activation of formyl-peptide receptor-like 1 and P2X7. J Immunol 2006, 5:3044-3052.
60. Nishimura M, Abiko Y, Kusano K, Yamazaki M, Saitoh M, Mizoguchi I, Jinbu Y, Noguchi T, Kaku T. Localization of human beta-defensin 3 mRNA in normal oral epithelium, leukoplakia, and lichen planus: an in situ hybridization study. Med Electron Microsc 2003, 2:94-97.
61. Niyonsaba F, Hirata M, Ogawa H, Nagaoka I. Epithelial cell-derived antibacterial peptides human beta-defensins and cathelicidin: multifunctional activities on mast cells. Curr Drug Targets Inflamm Allergy 2003, 3:224-231.
62. Niyonsaba F, Iwabuchi K, Someya A, Hirata M, Matsuda H, Ogawa H, Nagaoka I. A cathelicidin family of human antibacterial peptide LL-37 induces mast cell chemotaxis. Immunology 2002, 1:20-26.
63. Niyonsaba F, Ogawa H, Nagaoka I. Human beta-defensin-2 functions as a chemotactic agent for tumour necrosis factor-alpha-treated human neutrophils. Immunology 2004, 3:273-281.
64. Niyonsaba F, Someya A, Hirata M, Ogawa H, Nagaoka I. Evaluation of the effects of peptide antibiotics human beta-defensins-1/-2 and LL-37 on histamine release and prostaglandin D(2) production from mast cells. Eur J Immunol 2001, 4:1066-1075.
65. Niyonsaba F, Ushio H, Nakano N, Ng W, Sayama K, Hashimoto K, Nagaoka I, Okumura K, Ogawa H. Antimicrobial peptides human beta-defensins stimulate epidermal keratinocyte migration, proliferation and production of proinflammatory cytokines and chemokines. J Invest Dermatol 2007, 3:594-604.
66. Nomura I, Goleva E, Howell MD, Hamid QA, Ong PY, Hall CF, Darst MA, Gao B, Boguniewicz M, Travers JB, Leung DY. Cytokine milieu of atopic dermatitis, as compared to psoriasis, skin prevents induction of innate immune response genes. J Immunol 2003, 6:3262-3269.
67. O'Neil DA, Porter EM, Elewaut D, Anderson GM, Eckmann L, Ganz T, Kagnoff MF. Expression and regulation of the human beta-defensins hBD-1 and hBD-2 in intestinal epithelium. J Immunol 1999, 12:6718-6724.
68. Ong PY, Ohtake T, Brandt C, Strickland I, Boguniewicz M, Ganz T, Gallo RL, Leung DY. Endogenous antimicrobial peptides and skin infections in atopic dermatitis. N Engl J Med 2002, 15:1151-1160. [see comments.]
69. Oppenheim FG, Xu T, McMillian FM, Levitz SM, Diamond RD, Offner GD, Troxler RF. Histatins, a novel family of histidine-rich proteins in human parotid secretion. Isolation, characterization, primary structure, and fungistatic effects on Candida albicans. J Biol Chem 1988, 16:7472-7477.
70. Paulsen F, Pufe T, Conradi L, Varoga D, Tsokos M, Papendieck J, Petersen W. Antimicrobial peptides are expressed and produced in healthy and inflamed human synovial membranes. J Pathol 2002, 3:369-377.
71. Porgador A, Irvine KR, Iwasaki A, Barber BH, Restifo NP, Germain RN. Predominant role for directly transfected dendritic cells in antigen presentation to CD8+ T cells after gene gun immunization. J Exp Med 1998, 6:1075-1082.
72. Quinones-Mateu ME, Lederman MM, Feng Z, Chakraborty B, Weber J, Rangel HR, Marotta ML, Mirza M, Jiang B, Kiser P, Medvik K, Sieg SF, Weinberg A. Human epithelial beta-defensins 2 and 3 inhibit HIV-1 replication. AIDS 2003, 16:F39-F48.
73. Ross KF, Herzberg MC. Calprotectin expression by gingival epithelial cells. Infect Immun 2001, 5:3248-3254.
74. Sahasrabudhe KS, Kimball JR, Morton TH, Weinberg A, Dale BA. Expression of the antimicrobial peptide, human beta-defensin 1, in duct cells of minor salivary glands and detection in saliva. J Dent Res 2000, 9:1669-1674.
75. Schonwetter BS, Stolzenberg ED, Zasloff MA. Epithelial antibiotics induced at sites of inflammation. Science 1995, 5204:1645-1648.
76. Schutte BC, Mitros JP, Bartlett JA, Walters JD, Jia HP, Welsh MJ, Casavant TL, McCray PB. Discovery of five conserved beta-defensin gene clusters using a computational search strategy. Proc Natl Acad Sci U S A 2002, 4:2129-2133.
77. Scott MG, Davidson DJ, Gold MR, Bowdish D, Hancock RE. The human antimicrobial peptide LL-37 is a multifunctional modulator of innate immune responses. J Immunol 2002, 7:3883-3891.
78. Scott MG, Dullaghan E, Mookherjee N, Glavas N, Waldbrook M, Thompson A, Wang A, Lee K, Doria S, Hamill P, Yu JJ, Li Y, Donini O, Guarna MM, Finlay BB, North JR, Hancock RE. An anti-infective peptide that selectively modulates the innate immune response. Nat Biotechnol 2007, 4:465-472.
79. Scott MG, Vreugdenhil AC, Buurman WA, Hancock RE, Gold MR. Cutting edge: cationic antimicrobial peptides block the binding of lipopolysaccharide (LPS) to LPS binding protein. J Immunol 2000, 2:549-553.
80. Shugars DC, Wahl SM. The role of the oral environment in HIV-1 transmission. J Am Dent Assoc 1998, 7:851-858.
81. Shugars DC, Watkins CA, Cowen HJ. Salivary concentration of secretory leukocyte protease inhibitor, an antimicrobial protein, is decreased with advanced age. Gerontology 2001, 5:246-253.
82. Sohnle PG, Hunter MJ, Hahn B, Chazin WJ. Zinc-reversible antimicrobial activity of recombinant calprotectin (migration inhibitory factor-related proteins 8 and 14). J Infect Dis 2000, 4:1272-1275.
83. Sorensen OE, Cowland JB, Theilgaard-Monch K, Liu L, Ganz T, Borregaard N. Wound healing and expression of antimicrobial peptides/polypeptides in human keratinocytes, a consequence of common growth factors. J Immunol 2003, 11:5583-5589.
84. Tani K, Murphy WJ, Chertov O, Salcedo R, Koh CY, Utsunomiya I, Funakoshi S, Asai O, Herrmann SH, Wang JM, Kwak LW, Oppenheim JJ. Defensins act as potent adjuvants that promote cellular and humoral immune responses in mice to a lymphoma idiotype and carrier antigens. Int Immunol 2000, 5:691-700.
85. Tarnawski A, Szabo IL, Husain SS, Soreghan B. Regeneration of gastric mucosa during ulcer healing is triggered by growth factors and signal transduction pathways. J Physiol Paris 2001, 6:337-344.
86. Territo MC, Ganz T, Selsted ME, Lehrer R. Monocyte-chemotactic activity of defensins from human neutrophils. J Clin Invest 1989, 6:2017-2020.
87. Tjabringa GS, Aarbiou J, Ninaber DK, Drijfhout JW, Sorensen OE, Borregaard N, Rabe KF, Hiemstra PS. The antimicrobial peptide LL-37 activates innate immunity at the airway epithelial surface by transactivation of the epidermal growth factor receptor. J Immunol 2003, 12:6690-6696.
88. 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. Induction of keratinocyte migration via transactivation of the epidermal growth factor receptor by the antimicrobial peptide LL-37. J Immunol 2005, 7:4662-4668.
89. van Wetering S, Manness-Lazeroms SP, van Sterkenburg MA, Daha MR, Dijkman JH, PS H. Effect of defensins on interleukin-8 synthesis in airway epithelial cells. Am J Physiol 1997, 272:L888-L896.
90. van Wetering S, Sterk PJ, Rabe KF, Hiemstra PS. Defensins: key players or bystanders in infection, injury, and repair in the lung? J Allergy Clin Immunol 1999, 6:1131-1138.
91. Varoga D, Pufe T, Harder J, Schroder JM, Mentlein R, Meyer-Hoffert U, Goldring MB, Tillmann B, Hassenpflug J, Paulsen F. Human beta-defensin 3 mediates tissue remodeling processes in articular cartilage by increasing levels of metalloproteinases and reducing levels of their endogenous inhibitors. Arthritis Rheum 2005, 6:1736-1745.
92. Wahl SM, McNeely TB, Janoff EN, Shugars D, Worley P, Tucker C, Orenstein JM. Secretory leukocyte protease inhibitor (SLPI) in mucosal fluids inhibits HIV-I. Oral Dis 1997, 3(Suppl. 1):S64-S69.
93. Wehkamp J, Fellermann K, Herrlinger KR, Baxmann S, Schmidt K, Schwind B, Duchrow M, Wohlschlager C, Feller AC, Stange EF. Human beta-defensin 2 but not beta-defensin 1 is expressed preferentially in colonic mucosa of inflammatory bowel disease. Eur J Gastroenterol Hepatol 2002, 7:745-752.
94. Weinberg A, Krisanaprakornkit S, Dale BA. Epithelial antimicrobial peptides: review and significance for oral applications. Crit Rev Oral Biol Med 1998, 4:399-414.
95. Westerlund U, Ingman T, Lukinmaa PL, Salo T, Kjeldsen L, Borregaard N, Tjaderhane L, Konttinen YT, Sorsa T. Human neutrophil gelatinase and associated lipocalin in adult and localized juvenile periodontitis. J Dent Res 1996, 8:1553-1563.
96. Wu Z, Hoover DM, Yang D, Boulegue C, Santamaria F, Oppenheim JJ, Lubkowski J, Lu W. Engineering disulfide bridges to dissect antimicrobial and chemotactic activities of human beta-defensin 3. Proc Natl Acad Sci U S A 2003, 15:8880-8885.
97. Yang D, Chen Q, Chertov O, Oppenheim JJ. Human neutrophil defensins selectively chemoattract naive T and immature dendritic cells. J Leukoc Biol 2000, 1:9-14.
98. Yang D, Chertov O, Bykovskaia SN, Chen Q, Buffo MJ, Shogan J, Anderson M, Schroder JM, Wang JM, Howard OM, Oppenheim JJ. Beta-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6. Science 1999, 5439:525-528.
99. Yang D, Chertov O, Oppenheim JJ. Participation of mammalian defensins and cathelicidins in anti-microbial immunity: receptors and activities of human defensins and cathelicidin (LL-37). J Leukoc Biol 2001, 5:691-697.
100. Yu J, Mookherjee N, Wee K, Bowdish DM, Pistolic J, Li Y, Rehaume L, Hancock RE. Host defense peptide LL-37, in synergy with inflammatory mediator IL-1beta, augments immune responses by multiple pathways. J Immunol 2007, 11:7684-7691.
101. Zanetti M. Cathelicidins, multifunctional peptides of the innate immunity. J Leukoc Biol 2004, 1:39-48.
102. Zasloff M. Antimicrobial peptides of multicellular organisms. Nature 2002, 6870:389-395.
103. Zhao C, Wang I, Lehrer RI. Widespread expression of beta-defensin hBD-1 in human secretory glands and epithelial cells. FEBS Lett 1996, 3:319-322.
104. Zuyderduyn S, Ninaber DK, Hiemstra PS, Rabe KF. The antimicrobial peptide LL-37 enhances IL-8 release by human airway smooth muscle cells. J Allergy Clin Immunol 2006, 6:1328-1335.