Defensins: "Simple" antimicrobial peptides or broad-spectrum molecules?

Cytokine and Growth Factor Reviews

Volumn 26, Issue 3, 2015, Pages 361-370

  Suarez Carmona, Meggy ^a   Hubert, Pascale ^a   Delvenne, Philippe ^a   Herfs, Michael ^a  

^a UNIVERSITY OF LIÈGE   (Belgium)

Author keywords

Biomarker; Carcinogenesis; Defensin; Immune system

Indexed keywords

ALPHA DEFENSIN; BETA DEFENSIN; DEFENSIN; SERINE ARGININE RICH PROTEIN; BIOLOGICAL MARKER;

ADAPTIVE IMMUNITY; ANGIOGENESIS; ANTIMICROBIAL ACTIVITY; CANCER GROWTH; CARCINOGENESIS; EPITHELIUM CELL; GENETIC VARIABILITY; HUMAN; IMMUNOMODULATION; INFLAMMATION; INNATE IMMUNITY; LYMPHANGIOGENESIS; MALE FERTILITY; NEUTROPHIL; NONHUMAN; PRIORITY JOURNAL; PROTEIN CONFORMATION; PROTEIN EXPRESSION; PROTEIN SYNTHESIS; SHORT SURVEY; TUMOR MICROENVIRONMENT; WOUND HEALING; ANIMAL; FERTILITY; IMMUNOLOGY; METABOLISM;

VERTEBRATA;

ADAPTIVE IMMUNITY; ANIMALS; BIOMARKERS; CARCINOGENESIS; DEFENSINS; FERTILITY; HUMANS; INFLAMMATION; LYMPHANGIOGENESIS; WOUND HEALING;

EID: 84929656366     PISSN: 13596101     EISSN: 18790305     Source Type: Journal    
DOI: 10.1016/j.cytogfr.2014.12.005     Document Type: Short Survey

References (131)

1. Liu L., Zhao C., Heng H.H., Ganz T. The human beta-defensin-1 and alpha-defensins are encoded by adjacent genes: two peptide families with differing disulfide topology share a common ancestry. Genomics 1997, 43:316-320.
2. Ganz T. Defensins: antimicrobial peptides of innate immunity. Nat Rev Immunol 2003, 3:710-720.
3. Quayle A.J., Porter E.M., Nussbaum A.A., Wang Y.M., Brabec C., Yip K.P., et al. Gene expression, immunolocalization, and secretion of human defensin-5 in human female reproductive tract. Am J Pathol 1998, 152:1247-1258.
4. Frye M., Bargon J., Dauletbaev N., Weber A., Wagner T.O., Gropp R. Expression of human alpha-defensin 5 (HD5) mRNA in nasal and bronchial epithelial cells. J Clin Pathol 2000, 53:770-773.
5. Frye M., Bargon J., Lembcke B., Wagner T.O., Gropp R. Differential expression of human alpha- and beta-defensins mRNA in gastrointestinal epithelia. Eur J Clin Invest 2000, 30:695-701.
6. Schutte B.C., Mitros J.P., Bartlett J.A., Walters J.D., Jia H.P., Welsh M.J., et al. Discovery of five conserved beta-defensin gene clusters using a computational search strategy. Proc Natl Acad Sci U S A 2002, 99:2129-2133.
7. Klotman M.E., Chang T.L. Defensins in innate antiviral immunity. Nat Rev Immunol 2006, 6:447-456.
8. Yamaguchi Y., Nagase T., Makita R., Fukuhara S., Tomita T., Tominaga T., et al. Identification of multiple novel epididymis-specific beta-defensin isoforms in humans and mice. J Immunol 2002, 169:2516-2523.
9. Tollner T.L., Venners S.A., Hollox E.J., Yudin A.I., Liu X., Tang G., et al. A common mutation in the defensin DEFB126 causes impaired sperm function and subfertility. Sci Transl Med 2011, 3. 92ra65.
10. Yu H., Dong J., Gu Y., Liu H., Xin A., Shi H., et al. The novel human beta-defensin 114 regulates lipopolysaccharide (LPS)-mediated inflammation and protects sperm from motility loss. J Biol Chem 2013, 288:12270-12282.
11. Yenugu S., Hamil K.G., Radhakrishnan Y., French F.S., Hall S.H. The androgen-regulated epididymal sperm-binding protein, human beta-defensin 118 (DEFB118) (formerly ESC42), is an antimicrobial beta-defensin. Endocrinology 2004, 145:3165-3173.
12. Daher K.A., Lehrer R.I., Ganz T., Kronenberg M. Isolation and characterization of human defensin cDNA clones. Proc Natl Acad Sci U S A 1988, 85:7327-7331.
13. Michaelson D., Rayner J., Couto M., Ganz T. Cationic defensins arise from charge-neutralized propeptides: a mechanism for avoiding leukocyte autocytotoxicity?. J Leukoc Biol 1992, 51:634-639.
14. Valore E.V., Martin E., Harwig S.S., Ganz T. Intramolecular inhibition of human defensin HNP-1 by its propiece. J Clin Invest 1996, 97:1624-1629.
15. Tongaonkar P., Golji A.E., Tran P., Ouellette A.J., Selsted M.E. High fidelity processing and activation of the human alpha-defensin HNP1 precursor by neutrophil elastase and proteinase 3. PLOS ONE 2012, 7:e32469.
16. Gabay J.E., Almeida R.P. Antibiotic peptides and serine protease homologs in human polymorphonuclear leukocytes: defensins and azurocidin. Curr Opin Immunol 1993, 5:97-102.
17. Ganz T., Lehrer R.I. Defensins. Curr Opin Immunol 1994, 6:584-589.
18. Panyutich A.V., Panyutich E.A., Krapivin V.A., Baturevich E.A., Ganz T. Plasma defensin concentrations are elevated in patients with septicemia or bacterial meningitis. J Lab Clin Med 1993, 122:202-207.
19. Vaschetto R., Grinstein J., Del Sorbo L., Khine A.A., Voglis S., Tullis E., et al. Role of human neutrophil peptides in the initial interaction between lung epithelial cells and CD4+ lymphocytes. J Leukoc Biol 2007, 81:1022-1031.
20. Ghosh D., Porter E., Shen B., Lee S.K., Wilk D., Drazba J., et al. Paneth cell trypsin is the processing enzyme for human defensin-5. Nat Immunol 2002, 3:583-590.
21. Valore E.V., Park C.H., Quayle A.J., Wiles K.R., McCray P.B., Ganz T. Human beta-defensin-1: an antimicrobial peptide of urogenital tissues. J Clin Invest 1998, 101:1633-1642.
22. Wilson C.L., Schmidt A.P., Pirila E., Valore E.V., Ferri N., Sorsa T., et al. Differential processing of {alpha}- and {beta}-defensin precursors by matrix metalloproteinase-7 (MMP-7). J Biol Chem 2009, 284:8301-8311.
23. Selsted M.E., Ouellette A.J. Mammalian defensins in the antimicrobial immune response. Nat Immunol 2005, 6:551-557.
24. Wu Z., Hoover D.M., Yang D., Boulegue C., Santamaria F., Oppenheim J.J., et al. Engineering disulfide bridges to dissect antimicrobial and chemotactic activities of human beta-defensin 3. Proc Natl Acad Sci U S A 2003, 100:8880-8885.
25. Ding J., Tasker C., Valere K., Sihvonen T., Descalzi-Montoya D.B., Lu W., et al. Anti-HIV activity of human defensin 5 in primary CD4+ T cells under serum-deprived conditions is a consequence of defensin-mediated cytotoxicity. PLOS ONE 2013, 8:e76038.
26. Schroeder B.O., Stange E.F., Wehkamp J. Waking the wimp: redox-modulation activates human beta-defensin 1. Gut Microbes 2011, 2:262-266.
27. Porter E., Yang H., Yavagal S., Preza G.C., Murillo O., Lima H., et al. Distinct defensin profiles in Neisseria gonorrhoeae and Chlamydia trachomatis urethritis reveal novel epithelial cell-neutrophil interactions. Infect Immun 2005, 73:4823-4833.
28. Wehkamp J., Wang G., Kubler I., Nuding S., Gregorieff A., Schnabel A., et al. The Paneth cell alpha-defensin deficiency of ileal Crohn's disease is linked to Wnt/Tcf-4. J Immunol 2007, 179:3109-3118.
29. Farin H.F., Karthaus W.R., Kujala P., Rakhshandehroo M., Schwank G., Vries R.G., et al. Paneth cell extrusion and release of antimicrobial products is directly controlled by immune cell-derived IFN-gamma. J Exp Med 2014, 211:1393-1405.
30. Suarez-Carmona M., Hubert P., Gonzalez A., Duray A., Roncarati P., Erpicum C., et al. DeltaNp63 isoform-mediated beta-defensin family up-regulation is associated with (lymph)angiogenesis and poor prognosis in patients with squamous cell carcinoma. Oncotarget 2014, 5:1856-1868.
31. Sorensen O.E., Thapa D.R., Rosenthal A., Liu L., Roberts A.A., Ganz T. Differential regulation of beta-defensin expression in human skin by microbial stimuli. J Immunol 2005, 174:4870-4879.
32. Garcia J.R., Krause A., Schulz S., Rodriguez-Jimenez F.J., Kluver E., Adermann K., et al. Human beta-defensin 4: a novel inducible peptide with a specific salt-sensitive spectrum of antimicrobial activity. FASEB J 2001, 15:1819-1821.
33. Johnston A., Gudjonsson J.E., Aphale A., Guzman A.M., Stoll S.W., Elder J.T. EGFR and IL-1 signaling synergistically promote keratinocyte antimicrobial defenses in a differentiation-dependent manner. J Invest Dermatol 2011, 131:329-337.
34. Shuyi Y., Feng W., Jing T., Hongzhang H., Haiyan W., Pingping M., et al. Human beta-defensin-3 (hBD-3) upregulated by LPS via epidermal growth factor receptor (EGFR) signaling pathways to enhance lymphatic invasion of oral squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2011, 112:616-625.
35. Froy O. Regulation of mammalian defensin expression by Toll-like receptor-dependent and independent signalling pathways. Cell Microbiol 2005, 7:1387-1397.
36. Harder J., Meyer-Hoffert U., Wehkamp K., Schwichtenberg L., Schroder J.M. Differential gene induction of human beta-defensins (hBD-1, -2, -3, and -4) in keratinocytes is inhibited by retinoic acid. J Invest Dermatol 2004, 123:522-529.
37. Yeaman M.R., Yount N.Y. Mechanisms of antimicrobial peptide action and resistance. Pharmacol Rev 2003, 55:27-55.
38. Cobo E., Chadee K. Antimicrobial human β-defensins in the colon and their role in infectious and non-infectious diseases. Pathogens 2013, 2:177-192.
39. Wang W., Owen S.M., Rudolph D.L., Cole A.M., Hong T., Waring A.J., et al. Activity of alpha- and theta-defensins against primary isolates of HIV-1. J Immunol 2004, 173:515-520.
40. Kim C., Gajendran N., Mittrucker H.W., Weiwad M., Song Y.H., Hurwitz R., et al. Human alpha-defensins neutralize anthrax lethal toxin and protect against its fatal consequences. Proc Natl Acad Sci U S A 2005, 102:4830-4835.
41. Chang T.L., Vargas J., DelPortillo A., Klotman M.E. Dual role of alpha-defensin-1 in anti-HIV-1 innate immunity. J Clin Invest 2005, 115:765-773.
42. Buck C.B., Day P.M., Thompson C.D., Lubkowski J., Lu W., Lowy D.R., et al. Human alpha-defensins block papillomavirus infection. Proc Natl Acad Sci U S A 2006, 103:1516-1521.
43. Guo C.J., Tan N., Song L., Douglas S.D., Ho W.Z. Alpha-defensins inhibit HIV infection of macrophages through upregulation of CC-chemokines. AIDS 2004, 18:1217-1218.
44. Smith J.G., Silvestry M., Lindert S., Lu W., Nemerow G.R., Stewart P.L. Insight into the mechanisms of adenovirus capsid disassembly from studies of defensin neutralization. PLoS Pathog 2010, 6:e1000959.
45. Klotman M.E., Rapista A., Teleshova N., Micsenyi A., Jarvis G.A., Lu W., et al. Neisseria gonorrhoeae-induced human defensins 5 and 6 increase HIV infectivity: role in enhanced transmission. J Immunol 2008, 180:6176-6185.
46. Rapista A., Ding J., Benito B., Lo Y.T., Neiditch M.B., Lu W., et al. Human defensins 5 and 6 enhance HIV-1 infectivity through promoting HIV attachment. Retrovirology 2011, 8:45.
47. Furci L., Tolazzi M., Sironi F., Vassena L., Lusso P. Inhibition of HIV-1 infection by human alpha-defensin-5, a natural antimicrobial peptide expressed in the genital and intestinal mucosae. PLOS ONE 2012, 7:e45208.
48. Yang D., Chertov O., Bykovskaia S.N., Chen Q., Buffo M.J., Shogan J., et al. Beta-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6. Science 1999, 286:525-528.
49. Rohrl J., Yang D., Oppenheim J.J., Hehlgans T. Human beta-defensin 2 and 3 and their mouse orthologs induce chemotaxis through interaction with CCR2. J Immunol 2010, 184:6688-6694.
50. Grigat J., Soruri A., Forssmann U., Riggert J., Zwirner J. Chemoattraction of macrophages T lymphocytes, and mast cells is evolutionarily conserved within the human alpha-defensin family. J Immunol 2007, 179:3958-3965.
51. Funderburg N., Lederman M.M., Feng Z., Drage M.G., Jadlowsky J., Harding C.V., et al. Human-defensin-3 activates professional antigen-presenting cells via Toll-like receptors 1 and 2. Proc Natl Acad Sci U S A 2007, 104:18631-18635.
52. Biragyn A., Ruffini P.A., Leifer C.A., Klyushnenkova E., Shakhov A., Chertov O., et al. Toll-like receptor 4-dependent activation of dendritic cells by beta-defensin 2. Science 2002, 298:1025-1029.
53. Tewary P., de la Rosa G., Sharma N., Rodriguez L.G., Tarasov S.G., Howard O.M., et al. β-Defensin 2 and 3 promote the uptake of self or CpG DNA, enhance IFN-alpha production by human plasmacytoid dendritic cells, and promote inflammation. J Immunol 2013, 191:865-874.
54. Ferris L.K., Mburu Y.K., Mathers A.R., Fluharty E.R., Larregina A.T., Ferris R.L., et al. Human beta-defensin 3 induces maturation of human Langerhans cell-like dendritic cells: an antimicrobial peptide that functions as an endogenous adjuvant. J Invest Dermatol 2013, 133:460-468.
55. Boniotto M., Jordan W.J., Eskdale J., Tossi A., Antcheva N., Crovella S., et al. Human beta-defensin 2 induces a vigorous cytokine response in peripheral blood mononuclear cells. Antimicrob Agents Chemother 2006, 50:1433-1441.
56. Lu W., de Leeuw E. Pro-inflammatory and pro-apoptotic properties of Human Defensin 5. Biochem Biophys Res Commun 2013, 436:557-562.
57. Chaly Y.V., Paleolog E.M., Kolesnikova T.S., Tikhonov I.I., Petratchenko E.V., Voitenok N.N. Neutrophil alpha-defensin human neutrophil peptide modulates cytokine production in human monocytes and adhesion molecule expression in endothelial cells. Eur Cytokine Netw 2000, 11:257-266.
58. Hashimoto S., Uto H., Kanmura S., Sakiyama T., Oku M., Iwashita Y., et al. Human neutrophil peptide-1 aggravates dextran sulfate sodium-induced colitis. Inflamm Bowel Dis 2012, 18:667-675.
59. Motzkus D., Schulz-Maronde S., Heitland A., Schulz A., Forssmann W.G., Jubner M., et al. The novel beta-defensin DEFB123 prevents lipopolysaccharide-mediated effects in vitro and in vivo. FASEB J 2006, 20:1701-1702.
60. Baroni A., Donnarumma G., Paoletti I., Longanesi-Cattani I., Bifulco K., Tufano M.A., et al. Antimicrobial human beta-defensin-2 stimulates migration, proliferation and tube formation of human umbilical vein endothelial cells. Peptides 2009, 30:267-272.
61. Jin G., Kawsar H.I., Hirsch S.A., Zeng C., Jia X., Feng Z., et al. An antimicrobial peptide regulates tumor-associated macrophage trafficking via the chemokine receptor CCR2, a model for tumorigenesis. PLoS ONE 2010, 5:e10993.
62. Petrov V., Funderburg N., Weinberg A., Sieg S. Human beta defensin-3 induces chemokines from monocytes and macrophages: diminished activity in cells from HIV-infected persons. Immunology 2013, 140:413-420.
63. Conejo-Garcia J.R., Benencia F., Courreges M.C., Kang E., Mohamed-Hadley A., Buckanovich R.J., et al. Tumor-infiltrating dendritic cell precursors recruited by a beta-defensin contribute to vasculogenesis under the influence of Vegf-A. Nat Med 2004, 10:950-958.
64. Rohrl J., Huber B., Koehl G.E., Geissler E.K., Hehlgans T. Mouse beta-defensin 14 (Defb14) promotes tumor growth by inducing angiogenesis in a CCR6-dependent manner. J Immunol 2012, 188:4931-4939.
65. Economopoulou M., Bdeir K., Cines D.B., Fogt F., Bdeir Y., Lubkowski J., et al. Inhibition of pathologic retinal neovascularization by alpha-defensins. Blood 2005, 106:3831-3838.
66. Chavakis T., Cines D.B., Rhee J.S., Liang O.D., Schubert U., Hammes H.P., et al. Regulation of neovascularization by human neutrophil peptides (alpha-defensins): a link between inflammation and angiogenesis. FASEB J 2004, 18:1306-1308.
67. Hubert P., Herman L., Roncarati P., Maillard C., Renoux V., Demoulin S., et al. Altered alpha-defensin 5 expression in cervical squamocolumnar junction: implication in the formation of a viral/tumour-permissive microenvironment. J Pathol 2014, 234:464-477.
68. Roupe K.M., Nybo M., Sjobring U., Alberius P., Schmidtchen A., Sorensen O.E. Injury is a major inducer of epidermal innate immune responses during wound healing. J Invest Dermatol 2010, 130:1167-1177.
69. Galkowska H., Olszewski W.L., Wojewodzka U. Expression of natural antimicrobial peptide beta-defensin-2 and Langerhans cell accumulation in epidermis from human non-healing leg ulcers. Folia Histochem Cytobiol 2005, 43:133-136.
70. Lan C.C., Wu C.S., Huang S.M., Kuo H.Y., Wu I.H., Liang C.W., et al. High-glucose environment reduces human beta-defensin-2 expression in human keratinocytes: implications for poor diabetic wound healing. Br J Dermatol 2012, 166:1221-1229.
71. Niyonsaba F., Ushio H., Nakano N., Ng W., Sayama K., Hashimoto K., et al. Antimicrobial peptides human beta-defensins stimulate epidermal keratinocyte migration, proliferation and production of proinflammatory cytokines and chemokines. J Invest Dermatol 2007, 127:594-604.
72. Hirsch T., Spielmann M., Zuhaili B., Fossum M., Metzig M., Koehler T., et al. Human beta-defensin-3 promotes wound healing in infected diabetic wounds. J Gene Med 2009, 11:220-228.
73. Otte J.M., Werner I., Brand S., Chromik A.M., Schmitz F., Kleine M., et al. Human beta defensin 2 promotes intestinal wound healing in vitro. J Cell Biochem 2008, 104:2286-2297.
74. Sheng Q., Lv Z., Cai W., Song H., Qian L., Mu H., et al. Human beta-defensin-3 promotes intestinal epithelial cell migration and reduces the development of necrotizing enterocolitis in a neonatal rat model. Pediatr Res 2014, 76:269-279.
75. Patil A.A., Cai Y., Sang Y., Blecha F., Zhang G. Cross-species analysis of the mammalian beta-defensin gene family: presence of syntenic gene clusters and preferential expression in the male reproductive tract. Physiol Genomics 2005, 23:5-17.
76. Zhou Y.S., Webb S., Lettice L., Tardif S., Kilanowski F., Tyrrell C., et al. Partial deletion of chromosome 8 beta-defensin cluster confers sperm dysfunction and infertility in male mice. PLoS Genet 2013, 9:e1003826.
77. Dube E., Hermo L., Chan P.T., Cyr D.G. Alterations in gene expression in the caput epididymides of nonobstructive azoospermic men. Biol Reprod 2008, 78:342-351.
78. Tollner T.L., Yudin A.I., Tarantal A.F., Treece C.A., Overstreet J.W., Cherr G.N. Beta-defensin 126 on the surface of macaque sperm mediates attachment of sperm to oviductal epithelia. Biol Reprod 2008, 78:400-412.
79. Tollner T.L., Yudin A.I., Treece C.A., Overstreet J.W., Cherr G.N. Macaque sperm coating protein DEFB126 facilitates sperm penetration of cervical mucus. Hum Reprod 2008, 23:2523-2534.
80. Yudin A.I., Generao S.E., Tollner T.L., Treece C.A., Overstreet J.W., Cherr G.N. Beta-defensin 126 on the cell surface protects sperm from immunorecognition and binding of anti-sperm antibodies. Biol Reprod 2005, 73:1243-1252.
81. Yudin A.I., Treece C.A., Tollner T.L., Overstreet J.W., Cherr G.N. The carbohydrate structure of DEFB126, the major component of the cynomolgus Macaque sperm plasma membrane glycocalyx. J Membr Biol 2005, 207:119-129.
82. Diao R., Fok K.L., Chen H., Yu M.K., Duan Y., Chung C.M., et al. Deficient human beta-defensin 1 underlies male infertility associated with poor sperm motility and genital tract infection. Sci Transl Med 2014, 6. 249ra108.
83. Zanich A., Pascall J.C., Jones R. Secreted epididymal glycoprotein 2D6 that binds to the sperm's plasma membrane is a member of the beta-defensin superfamily of pore-forming glycopeptides. Biol Reprod 2003, 69:1831-1842.
84. Zhou C.X., Zhang Y.L., Xiao L., Zheng M., Leung K.M., Chan M.Y., et al. An epididymis-specific beta-defensin is important for the initiation of sperm maturation. Nat Cell Biol 2004, 6:458-464.
85. Taudien S., Gabel G., Kuss O., Groth M., Grutzmann R., Huse K., et al. Association studies of the copy-number variable ss-defensin cluster on 8p23.1 in adenocarcinoma and chronic pancreatitis. BMC Res Notes 2012, 5:629.
86. Abe S., Miura K., Kinoshita A., Mishima H., Miura S., Yamasaki K., et al. Copy number variation of the antimicrobial-gene, defensin beta 4, is associated with susceptibility to cervical cancer. J Hum Genet 2013, 58:250-253.
87. Huse K., Taudien S., Groth M., Rosenstiel P., Szafranski K., Hiller M., et al. Genetic variants of the copy number polymorphic beta-defensin locus are associated with sporadic prostate cancer. Tumour Biol 2008, 29:83-92.
88. Park S.K., Yang J.J., Oh S., Cho L.Y., Ma S.H., Shin A., et al. Innate immunity and non-Hodgkin's lymphoma (NHL) related genes in a nested case-control study for gastric cancer risk. PLOS ONE 2012, 7:e45274.
89. Joly S., Compton L.M., Pujol C., Kurago Z.B., Guthmiller J.M. Loss of human beta-defensin 1, 2, and 3 expression in oral squamous cell carcinoma. Oral Microbiol Immunol 2009, 24:353-360.
90. Hu W., Bassig B.A., Xu J., Zheng T., Zhang Y., Berndt S.I., et al. Polymorphisms in pattern-recognition genes in the innate immunity system and risk of non-Hodgkin lymphoma. Environ Mol Mutagen 2013, 54:72-77.
91. Donald C.D., Sun C.Q., Lim S.D., Macoska J., Cohen C., Amin M.B., et al. Cancer-specific loss of beta-defensin 1 in renal and prostatic carcinomas. Lab Invest 2003, 83:501-505.
92. Shi N., Jin F., Zhang X., Clinton S.K., Pan Z., Chen T. Overexpression of human beta-defensin 2 promotes growth and invasion during esophageal carcinogenesis. Oncotarget 2014.
93. Kesting M.R., Loeffelbein D.J., Hasler R.J., Wolff K.D., Rittig A., Schulte M., et al. Expression profile of human beta-defensin 3 in oral squamous cell carcinoma. Cancer Invest 2009, 27:575-581.
94. Gunes M., Gecit I., Pirincci N., Kemik A.S., Purisa S., Ceylan K., et al. Plasma human neutrophil proteins-1, -2, and -3 levels in patients with bladder cancer. J Cancer Res Clin Oncol 2013, 139:195-199.
95. Albrethsen J., Moller C.H., Olsen J., Raskov H., Gammeltoft S. Human neutrophil peptides 1, 2 and 3 are biochemical markers for metastatic colorectal cancer. Eur J Cancer 2006, 42:3057-3064.
96. Albrethsen J., Bogebo R., Gammeltoft S., Olsen J., Winther B., Raskov H. Upregulated expression of human neutrophil peptides 1, 2 and 3 (HNP 1-3) in colon cancer serum and tumours: a biomarker study. BMC Cancer 2005, 5:8.
97. Han Q., Wang R., Sun C., Jin X., Liu D., Zhao X., et al. Human beta-defensin-1 suppresses tumor migration and invasion and is an independent predictor for survival of oral squamous cell carcinoma patients. PLOS ONE 2014, 9:e91867.
98. Gerashchenko O.L., Zhuravel E.V., Skachkova O.V., Khranovska N.N., Filonenko V.V., Pogrebnoy P.V., et al. Biologic activities of recombinant human-beta-defensin-4 toward cultured human cancer cells. Exp Oncol 2013, 35:76-82.
99. Barker E., Reisfeld R.A. A mechanism for neutrophil-mediated lysis of human neuroblastoma cells. Cancer Res 1993, 53:362-367.
100. McKeown S.T., Lundy F.T., Nelson J., Lockhart D., Irwin C.R., Cowan C.G., et al. The cytotoxic effects of human neutrophil peptide-1 (HNP1) and lactoferrin on oral squamous cell carcinoma (OSCC) in vitro. Oral Oncol 2006, 42:685-690.
101. Muller C.A., Markovic-Lipkovski J., Klatt T., Gamper J., Schwarz G., Beck H., et al. Human alpha-defensins HNPs-1, -2, and -3 in renal cell carcinoma: influences on tumor cell proliferation. Am J Pathol 2002, 160:1311-1324.
102. Mburu Y.K., Abe K., Ferris L.K., Sarkar S.N., Ferris R.L. Human beta-defensin 3 promotes NF-kappaB-mediated CCR7 expression and anti-apoptotic signals in squamous cell carcinoma of the head and neck. Carcinogenesis 2011, 32:168-174.
103. Hanahan D., Weinberg R.A. Hallmarks of cancer: the next generation. Cell 2011, 144:646-674.
104. Potente M., Gerhardt H., Carmeliet P. Basic and therapeutic aspects of angiogenesis. Cell 2011, 146:873-887.
105. Galon J., Costes A., Sanchez-Cabo F., Kirilovsky A., Mlecnik B., Lagorce-Pages C., et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 2006, 313:1960-1964.
106. Li D., Wang W., Shi H.S., Fu Y.J., Chen X., Chen X.C., et al. Gene therapy with beta-defensin 2 induces antitumor immunity and enhances local antitumor effects. Hum Gene Ther 2014, 25:63-72.
107. Hubert P., Herman L., Maillard C., Caberg J.H., Nikkels A., Pierard G., et al. Defensins induce the recruitment of dendritic cells in cervical human papillomavirus-associated (pre)neoplastic lesions formed in vitro and transplanted in vivo. FASEB J 2007, 21:2765-2775.
108. Wang Y.S., Li D., Shi H.S., Wen Y.J., Yang L., Xu N., et al. Intratumoral expression of mature human neutrophil peptide-1 mediates antitumor immunity in mice. Clin Cancer Res 2009, 15:6901-6911.
109. Yang D., Chen Q., Chertov O., Oppenheim J.J. Human neutrophil defensins selectively chemoattract naive T and immature dendritic cells. J Leukoc Biol 2000, 68:9-14.
110. Larmonier N., Marron M., Zeng Y., Cantrell J., Romanoski A., Sepassi M., et al. Tumor-derived CD4(+)CD25(+) regulatory T cell suppression of dendritic cell function involves TGF-beta and IL-10. Cancer Immunol Immunother 2007, 56:48-59.
111. Qian B.Z., Pollard J.W. New tricks for metastasis-associated macrophages. Breast Cancer Res 2012, 14:316.
112. Nam M.J., Kee M.K., Kuick R., Hanash S.M. Identification of defensin alpha6 as a potential biomarker in colon adenocarcinoma. J Biol Chem 2005, 280:8260-8265.
113. van den Broek I., Sparidans R.W., Engwegen J.Y., Cats A., Depla A.C., Schellens J.H., et al. Evaluation of human neutrophil peptide-1, -2 and -3 as serum markers for colorectal cancer. Cancer Biomark 2010, 7:109-115.
114. Kemik O., Kemik A.S., Sumer A., Begenik H., Purisa S., Tuzun S. Human neutrophil peptides 1, 2 and 3 (HNP 1-3): elevated serum levels in colorectal cancer and novel marker of lymphatic and hepatic metastasis. Hum Exp Toxicol 2013, 32:167-171.
115. Balluff B., Rauser S., Meding S., Elsner M., Schone C., Feuchtinger A., et al. MALDI imaging identifies prognostic seven-protein signature of novel tissue markers in intestinal-type gastric cancer. Am J Pathol 2011, 179:2720-2729.
116. Melle C., Ernst G., Schimmel B., Bleul A., Thieme H., Kaufmann R., et al. Discovery and identification of alpha-defensins as low abundant, tumor-derived serum markers in colorectal cancer. Gastroenterology 2005, 129:66-73.
117. Yamaguchi N., Isomoto H., Mukae H., Ishimoto H., Ohnita K., Shikuwa S., et al. Concentrations of alpha- and beta-defensins in plasma of patients with inflammatory bowel disease. Inflamm Res 2009, 58:192-197.
118. Kanmura S., Uto H., Numata M., Hashimoto S., Moriuchi A., Fujita H., et al. Human neutrophil peptides 1-3 are useful biomarkers in patients with active ulcerative colitis. Inflamm Bowel Dis 2009, 15:909-917.
119. Vordenbaumen S., Timm D., Bleck E., Richter J., Fischer-Betz R., Chehab G., et al. Altered serum levels of human neutrophil peptides (HNP) and human beta-defensin 2 (hBD2) in Wegener's granulomatosis. Rheumatol Int 2011, 31:1251-1254.
120. Cheng F.J., Zhou X.J., Zhao Y.F., Zhao M.H., Zhang H. Human neutrophil peptide 1-3, a component of the neutrophil extracellular trap, as a potential biomarker of lupus nephritis. Int J Rheum Dis 2014.
121. Etienne G., Dupouy M., Costaglioli P., Chollet C., Lagarde V., Pasquet J.M., et al. α-Defensin 1-3 and alpha-defensin 4 as predictive markers of imatinib resistance and relapse in CML patients. Dis Markers 2011, 30:221-227.
122. Arimura Y., Ashitani J., Yanagi S., Tokojima M., Abe K., Mukae H., et al. Elevated serum beta-defensins concentrations in patients with lung cancer. Anticancer Res 2004, 24:4051-4057.
123. Jansen P.A., Rodijk-Olthuis D., Hollox E.J., Kamsteeg M., Tjabringa G.S., de Jongh G.J., et al. Beta-defensin-2 protein is a serum biomarker for disease activity in psoriasis and reaches biologically relevant concentrations in lesional skin. PLoS ONE 2009, 4:e4725.
124. Garcia-Berrocoso T., Giralt D., Bustamante A., Llombart V., Rubiera M., Penalba A., et al. Role of beta-defensin 2 and interleukin-4 receptor as stroke outcome biomarkers. J Neurochem 2014, 129:463-472.
125. Winter J., Wenghoefer M. Human defensins: potential tools for clinical applications. Polymers 2012, 4:691-709.
126. Hazrati E., Galen B., Lu W., Wang W., Ouyang Y., Keller M.J., et al. Human alpha- and beta-defensins block multiple steps in herpes simplex virus infection. J Immunol 2006, 177:8658-8666.
127. Park H.J., Qin H., Cha S.C., Sharma R., Chung Y., Schluns K.S., et al. Induction of TLR4-dependent CD8+ T cell immunity by murine beta-defensin2 fusion protein vaccines. Vaccine 2011, 29:3476-3482.
128. Wenghoefer M., Pantelis A., Dommisch H., Reich R., Martini M., Allam J.P., et al. Decreased gene expression of human beta-defensin-1 in the development of squamous cell carcinoma of the oral cavity. Int J Oral Maxillofac Surg 2008, 37:660-663.
129. Radeva M.Y., Jahns F., Wilhelm A., Glei M., Settmacher U., Greulich K.O., et al. Defensin alpha 6 (DEFA 6) overexpression threshold of over 60 fold can distinguish between adenoma and fully blown colon carcinoma in individual patients. BMC Cancer 2010, 10:588.
130. Shestakova T., Zhuravel E., Bolgova L., Alekseenko O., Soldatkina M., Pogrebnoy P. Expression of human beta-defensins-1, 2 and 4 mRNA in human lung tumor tissue: a pilot study. Exp Oncol 2008, 30:153-156.
131. Gambichler T., Skrygan M., Huyn J., Bechara F.G., Sand M., Altmeyer P., et al. Pattern of mRNA expression of beta-defensins in basal cell carcinoma. BMC Cancer 2006, 6:163.