Defensins comprise one of the largest groups of host defence peptides, present throughout evolution, in fungi and flowering plants as well as in invertebrates and vertebrates. These cysteine-rich, cationic peptides have a common ability to kill a broad range of microorganisms including bacteria, yeast and viruses. As such, they are a strong component of the arsenal that is an organism’s innate immunity. It is becoming increasingly clear, however, that antimicrobial action is only one of the numerous roles of these multifunctional peptides. In recent years, the functions of defensins in immunomodulation have been widely investigated, and their involvement in other processes (such as fertility) is becoming evident. This review addresses recent advances in the immunomodulatory activity of β-defensins as well as the involvement of β-defensins in fertility, development, wound healing and cancer.

Keywords:
Antimicrobial peptides, Host defense, Toll-like receptor, Defensin
1.
Lynn DJ, Bradley DG: Discovery of alpha-defensins in basal mammals. Dev Comp Immunol 2007;31:963–967.
2.
Lehrer RI: Primate defensins. Nat Rev Microbiol 2004;2:727–738.
3.
Pazgier M, Hoover DM, Yang D, Lu W, Lubkowski J: Human beta-defensins. Cell Mol Life Sci 2006;63:1294–1313.
4.
Nguyen TX, Cole AM, Lehrer RI: Evolution of primate theta-defensins: a serpentine path to a sweet tooth. Peptides 2003;24:1647–1654.
5.
Schutte BC, Mitros JP, Bartlett JA, Walters JD, Jia HP, Welsh MJ, Casavant TL, McCray PB Jr: Discovery of five conserved beta-defensin gene clusters using a computational search strategy. Proc Natl Acad Sci USA 2002;99:2129–2133.
6.
Bauer F, Schweimer K, Kluver E, Conejo-Garcia JR, Forssmann WG, Rosch P, Adermann K, Sticht H: Structure determination of human and murine beta-defensins reveals structural conservation in the absence of significant sequence similarity. Protein Sci 2001;10:2470–2479.
7.
Morrison GM, Semple CA, Kilanowski FM, Hill RE, Dorin JR: Signal sequence conservation and mature peptide divergence within subgroups of the murine beta-defensin gene family. Mol Biol Evol 2003;20:460–470.
8.
Semple CA, Maxwell A, Gautier P, Kilanowski FM, Eastwood H, Barran PE, Dorin JR: The complexity of selection at the major primate beta-defensin locus. BMC Evol Biol 2005;5:32.
9.
Crovella S, Antcheva N, Zelezetsky I, Boniotto M, Pacor S, Verga Falzacappa MV, Tossi A: Primate beta-defensins – structure, function and evolution. Curr Protein Pept Sci 2005;6:7–21.
10.
Lai Y, Gallo RL: AMPed-up immunity: how antimicrobial peptides have multiple roles in immune defense. Trends Immunol 2009;30:131–141.
11.
Semple CA, Gautier P, Taylor K, Dorin JR: The changing of the guard: molecular diversity and rapid evolution of beta-defensins. Mol Divers 2006;10:575–584.
12.
Whittington CM, Papenfuss AT, Bansal P, Torres AM, Wong ES, Deakin JE, Graves T, Alsop A, Schatzkamer K, Kremitzki C, Ponting CP, Temple-Smith P, Warren WC, Kuchel PW, Belov K: Defensins and the convergent evolution of platypus and reptile venom genes. Genome Res 2008;18:986–994.
13.
Whittington CM, Papenfuss AT, Kuchel PW, Belov K: Expression patterns of platypus defensin and related venom genes across a range of tissue types reveal the possibility of broader functions for OvDLPs than previously suspected. Toxicon 2008;52:559–565.
14.
Abu BS, Hollox EJ, Armour JA: Allelic recombination between distinct genomic locations generates copy number diversity in human beta-defensins. Proc Natl Acad Sci USA 2009;106:853–858.
15.
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: Psoriasis is associated with increased beta-defensin genomic copy number. Nat Genet 2008;40:23–25.
16.
Fellermann K, Stange DE, Schaeffeler E, Schmalzl H, Wehkamp J, Bevins CL, Reinisch W, Teml A, Schwab M, Lichter P, Radlwimmer B, Stange EF: A chromosome 8 gene-cluster polymorphism with low human beta-defensin 2 gene copy number predisposes to Crohn’s disease of the colon. Am J Hum Genet 2006;79:439–448.
17.
Bentley RW, Pearson J, Gearry RB, Barclay ML, McKinney C, Merriman TR, Roberts RL: Association of higher DEFB4 genomic copy number with Crohn’s disease. Am J Gastroenterol 2010;105:354–359.
18.
Aldhous MC, Abu BS, Prescott NJ, Palla R, Soo K, Mansfield JC, Mathew CG, Satsangi J, Armour JA: Measurement methods and accuracy in copy number variation: failure to replicate associations of beta-defensin copy number with Crohn’s disease. Hum Mol Genet 2010;19:4930–4938.
19.
Peyrin-Biroulet L, Beisner J, Wang G, Nuding S, Oommen ST, Kelly D, Parmentier-Decrucq E, Dessein R, Merour E, Chavatte P, Grandjean T, Bressenot A, Desreumaux P, Colombel JF, Desvergne B, Stange EF, Wehkamp J, Chamaillard M: Peroxisome proliferator-activated receptor gamma activation is required for maintenance of innate antimicrobial immunity in the colon. Proc Natl Acad Sci USA 2010;107:8772–8777.
20.
Ozturk A, Famili P, Vieira AR: The antimicrobial peptide DEFB1 is associated with caries. J Dent Res 2010;89:631–636.
21.
Jurevic RJ, Bai M, Chadwick RB, White TC, Dale BA: Single-nucleotide polymorphisms (SNPs) in human beta-defensin 1: high-throughput SNP assays and association with Candida carriage in type I diabetics and nondiabetic controls. J Clin Microbiol 2003;41:90–96.
22.
Sass V, Schneider T, Wilmes M, Korner C, Tossi A, Novikova N, Shamova O, Sahl HG: Human beta-defensin 3 inhibits cell wall biosynthesis in staphylococci. Infect Immun 2010;78:2793–2800.
23.
Schneider T, Kruse T, Wimmer R, Wiedemann I, Sass V, Pag U, Jansen A, Nielsen AK, Mygind PH, Raventos DS, Neve S, Ravn B, Bonvin AM, De ML, Andersen AS, Gammelgaard LK, Sahl HG, Kristensen HH: Plectasin, a fungal defensin, targets the bacterial cell wall precursor lipid II. Science 2010;328:1168–1172.
24.
Wilson CL, Ouellette AJ, Satchell DP, Ayabe T, Lopez-Boado YS, Stratman JL, Hultgren SJ, Matrisian LM, Parks WC: Regulation of intestinal alpha-defensin activation by the metalloproteinase matrilysin in innate host defense. Science 1999;286:113–117.
25.
Salzman NH, Ghosh D, Huttner KM, Paterson Y, Bevins CL: Protection against enteric salmonellosis in transgenic mice expressing a human intestinal defensin. Nature 2003;422:522–526.
26.
Morrison G, Kilanowski F, Davidson D, Dorin J: Characterization of the mouse beta defensin 1, defb1, mutant mouse model. Infect Immun 2002;70:3053–3060.
27.
Moser C, Weiner DJ, Lysenko E, Bals R, Weiser JN, Wilson JM: Beta-defensin 1 contributes to pulmonary innate immunity in mice. Infect Immun 2002;70:3068–3072.
28.
Schroeder BO, Wu Z, Nuding S, Groscurth S, Marcinowski M, Beisner J, Buchner J, Schaller M, Stange EF, Wehkamp J: Reduction of disulphide bonds unmasks potent antimicrobial activity of human beta-defensin 1. Nature 2011;469:419–423.
29.
Seo ES, Blaum BS, Vargues T, De CM, Deakin JA, Lyon M, Barran PE, Campopiano DJ, Uhrin D: Interaction of human beta-defensin 2 (HBD2) with glycosaminoglycans. Biochemistry 2010;49:10486–10495.
30.
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;286:525–528.
31.
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 USA 2003;100:8880–8885.
32.
Taylor K, Clarke DJ, McCullough B, Chin W, Seo E, Yang D, Oppenheim J, Uhrin D, Govan JR, Campopiano DJ, Macmillan D, Barran PE, Dorin JR: Analysis and separation of residues important for the chemoattractant and antimicrobial activities of beta-defensin 3. J Biol Chem 2008;283:6631–6639.
33.
Rohrl J, Yang D, Oppenheim JJ, Hehlgans T: Identification and biological characterization of mouse beta-defensin 14 – the orthologue of human beta defensin 3. J Biol Chem 2007;283:5414–5419.
34.
Taylor K, Rolfe M, Reynolds N, Kilanowski F, Pathania U, Clarke D, Yang D, Oppenheim J, Samuel K, Howie S, Barran P, Macmillan D, Campopiano D, Dorin J: Defensin-related peptide 1 (Defr1) is allelic to Defb8 and chemoattracts immature DC and CD4+ T cells independently of CCR6. Eur J Immunol 2009;39:1353–1360.
35.
Rohrl J, Yang D, Oppenheim JJ, Hehlgans T: Human beta-defensin 2 and 3 and their mouse orthologs induce chemotaxis through interaction with CCR2. J Immunol 2010;184:6688–6694.
36.
Jin G, Kawsar HI, Hirsch SA, Zeng C, Jia X, Feng Z, Ghosh SK, Zheng QY, Zhou A, McIntyre TM, Weinberg A: An antimicrobial peptide regulates tumor-associated macrophage trafficking via the chemokine receptor CCR2, a model for tumorigenesis. PLoS One 2010;5:e10993.
37.
Biragyn A, Ruffini PA, Leifer CA, Klyushnenkova E, Shakhov A, Chertov O, Shirakawa AK, Farber JM, Segal DM, Oppenheim JJ, Kwak LW: Toll-like receptor 4-dependent activation of dendritic cells by beta-defensin 2. Science 2002;298:1025–1029.
38.
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 USA 2007;104:18631–18635.
39.
Funderburg NT, Jadlowsky JK, Lederman MM, Feng Z, Weinberg A, Sieg SF: The Toll-like receptor 1/2 agonists Pam(3) CSK(4) and human beta-defensin-3 differentially induce interleukin-10 and nuclear factor-kappaB signalling patterns in human monocytes. Immunology 2011;134:151–160.
40.
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;127:594–604.
41.
Niyonsaba F, Ushio H, Hara M, Yokoi H, Tominaga M, Takamori K, Kajiwara N, Saito H, Nagaoka I, Ogawa H, Okumura K: Antimicrobial peptides human beta-defensins and cathelicidin LL-37 induce the secretion of a pruritogenic cytokine IL-31 by human mast cells. J Immunol 2010;184:3526–3534.
42.
Nagaoka I, Niyonsaba F, Tsutsumi-Ishii Y, Tamura H, Hirata M: Evaluation of the effect of human beta-defensins on neutrophil apoptosis. Int Immunol 2008;20:543–553.
43.
Shi J, Aono S, Lu W, Ouellette AJ, Hu X, Ji Y, Wang L, Lenz S, van Ginkel FW, Liles M, Dykstra C, Morrison EE, Elson CO: A novel role for defensins in intestinal homeostasis: regulation of IL-1beta secretion. J Immunol 2007;179:1245–1253.
44.
Miles K, Clarke DJ, Lu W, Sibinska Z, Beaumont PE, Davidson DJ, Barr TA, Campopiano DJ, Gray M: Dying and necrotic neutrophils are anti-inflammatory secondary to the release of alpha-defensins. J Immunol 2009;183:2122–2132.
45.
Sorensen OE, Thapa DR, Rosenthal A, Liu L, Roberts AA, Ganz T: Differential regulation of beta-defensin expression in human skin by microbial stimuli. J Immunol 2005;174:4870–4879.
46.
Ryan LK, Dai J, Yin Z, Megjugorac N, Uhlhorn V, Yim S, Schwartz KD, Abrahams JM, Diamond G, Fitzgerald-Bocarsly P: Modulation of human beta-defensin-1 (hBD-1) in plasmacytoid dendritic cells (PDC), monocytes, and epithelial cells by influenza virus, Herpes simplex virus, and Sendai virus and its possible role in innate immunity. J Leukoc Biol 2011;90:343–356.
47.
Liu AY, Destoumieux D, Wong AV, Park CH, Valore EV, Liu L, Ganz T: Human beta-defensin-2 production in keratinocytes is regulated by interleukin-1, bacteria, and the state of differentiation. J Invest Dermatol 2002;118:275–281.
48.
Chadebech P, Goidin D, Jacquet C, Viac J, Schmitt D, Staquet MJ: Use of human reconstructed epidermis to analyze the regulation of beta-defensin hBD-1, hBD-2, and hBD-3 expression in response to LPS. Cell Biol Toxicol 2003;19:313–324.
49.
Garcia JR, Krause A, Schulz S, Rodriguez-Jimenez FJ, Kluver E, Adermann K, Forssmann U, Frimpong-Boateng A, Bals R, Forssmann WG: Human beta-defensin 4: a novel inducible peptide with a specific salt-sensitive spectrum of antimicrobial activity. FASEB J 2001;15:1819–1821.
50.
Gariboldi S, Palazzo M, Zanobbio L, Selleri S, Sommariva M, Sfondrini L, Cavicchini S, Balsari A, Rumio C: Low molecular weight hyaluronic acid increases the self-defense of skin epithelium by induction of beta-defensin 2 via TLR2 and TLR4. J Immunol 2008;181:2103–2110.
51.
Krisanaprakornkit S, Kimball JR, Dale BA: Regulation of human beta-defensin-2 in gingival epithelial cells: the involvement of mitogen-activated protein kinase pathways, but not the NF-kappaB transcription factor family. J Immunol 2002;168:316–324.
52.
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;110:121–124.
53.
Semple F, Webb S, Li HN, Patel HB, Perretti M, Jackson IJ, Gray M, Davidson DJ, Dorin JR: Human beta-defensin 3 has immunosuppressive activity in vitro and in vivo. Eur J Immunol 2010;40:1073–1078.
54.
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;169:3883–3891.
55.
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;347:1151–1160.
56.
Jansen PA, Rodijk-Olthuis D, Hollox EJ, Kamsteeg M, Tjabringa GS, de Jongh GJ, van Vlijmen-Willems IM, Bergboer JG, van Rossum MM, de Jong EM, den HM, Evers AW, Bergers M, Armour JA, Zeeuwen PL, Schalkwijk J: 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.
57.
Semple F, MacPherson H, Webb S, Cox SL, Mallin LJ, Tyrrell C, Grimes GR, Semple CA, Nix MA, Millhauser GL, Dorin JR: Human beta-defensin 3 affects the activity of pro-inflammatory pathways associated with MyD88 and TRIF. Eur J Immunol 2011;41:3291–3300.
58.
Di Nardo A, Braff MH, Taylor KR, Na C, Granstein RD, McInturff JE, Krutzik S, Modlin RL, Gallo RL: Cathelicidin antimicrobial peptides block dendritic cell TLR4 activation and allergic contact sensitization. J Immunol 2007;178:1829–1834.
59.
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: Modulation of the TLR-mediated inflammatory response by the endogenous human host defense peptide LL-37. J Immunol 2006;176:2455–2464.
60.
Motzkus D, Schulz-Maronde S, Heitland A, Schulz A, Forssmann WG, Jubner M, Maronde E: The novel beta-defensin DEFB123 prevents lipopolysaccharide-mediated effects in vitro and in vivo. FASEB J 2006;20:1701–1702.
61.
Pingel LC, Kohlgraf KG, Hansen CJ, Eastman CG, Dietrich DE, Burnell KK, Srikantha RN, Xiao X, Belanger M, Progulske-Fox A, Cavanaugh JE, Guthmiller JM, Johnson GK, Joly S, Kurago ZB, Dawson DV, Brogden KA: Human beta-defensin 3 binds to hemagglutinin B (rHagB), a non-fimbrial adhesin from Porphyromonas gingivalis, and attenuates a pro-inflammatory cytokine response. Immunol Cell Biol 2008;86:643–649.
62.
Hazrati E, Galen B, Lu W, Wang W, Ouyang Y, Keller MJ, Lehrer RI, Herold BC: Human alpha- and beta-defensins block multiple steps in herpes simplex virus infection. J Immunol 2006;177:8658–8666.
63.
Leikina E, Delanoe-Ayari H, Melikov K, Cho MS, Chen A, Waring AJ, Wang W, Xie Y, Loo JA, Lehrer RI, Chernomordik LV: Carbohydrate-binding molecules inhibit viral fusion and entry by crosslinking membrane glycoproteins. Nat Immunol 2005;6:995–1001.
64.
Howard M, Muchamuel T, Andrade S, Menon S: Interleukin 10 protects mice from lethal endotoxemia. J Exp Med 1993;177:1205–1208.
65.
Navid F, Boniotto M, Walker C, Ahrens K, Proksch E, Sparwasser T, Muller W, Schwarz T, Schwarz A: Induction of regulatory T cells by a murine beta-defensin. J Immunol 2012;188:735–743.
66.
Candille SI, Kaelin CB, Cattanach BM, Yu B, Thompson DA, Nix MA, Kerns JA, Schmutz SM, Millhauser GL, Barsh GS: A {beta}-defensin mutation causes black coat color in domestic dogs. Science 2007;318:1418–1423.
67.
Anderson TM, vonHoldt BM, Candille SI, Musiani M, Greco C, Stahler DR, Smith DW, Padhukasahasram B, Randi E, Leonard JA, Bustamante CD, Ostrander EA, Tang H, Wayne RK, Barsh GS: Molecular and evolutionary history of melanism in North American gray wolves. Science 2009;323:1339–1343.
68.
Hirsch T, Spielmann M, Zuhaili B, Fossum M, Metzig M, Koehler T, Steinau HU, Yao F, Onderdonk AB, Steinstraesser L, Eriksson E: Human beta-defensin-3 promotes wound healing in infected diabetic wounds. J Gene Med 2009;11:220–228.
69.
Vongsa RA, Zimmerman NP, Dwinell MB: CCR6 regulation of the actin cytoskeleton orchestrates human beta defensin-2- and CCL20-mediated restitution of colonic epithelial cells. J Biol Chem 2009;284:10034–10045.
70.
Baroni A, Donnarumma G, Paoletti I, Longanesi-Cattani I, Bifulco K, Tufano MA, Carriero MV: Antimicrobial human beta-defensin-2 stimulates migration, proliferation and tube formation of human umbilical vein endothelial cells. Peptides 2009;30:267–272.
71.
McDermott AM, Redfern RL, Zhang B, Pei Y, Huang L, Proske RJ: Defensin expression by the cornea: multiple signalling pathways mediate IL-1beta stimulation of hBD-2 expression by human corneal epithelial cells. Invest Ophthalmol Vis Sci 2003;44:1859–1865.
72.
Li P, Chan HC, He B, So SC, Chung YW, Shang Q, Zhang YD, Zhang YL: An antimicrobial peptide gene found in the male reproductive system of rats. Science 2001;291:1783–1785.
73.
Zaballos A, Villares R, Albar JP, Martinez A, Marquez G: Identification on mouse chromosome 8 of new beta-defensin genes with regionally specific expression in the male reproductive organ. J Biol Chem 2004;279:12421–12426.
74.
Yamaguchi Y, Nagase T, Makita R, Fukuhara S, Tomita T, Tominaga T, Kurihara H, Ouchi Y: Identification of multiple novel epididymis-specific beta-defensin isoforms in humans and mice. J Immunol 2002;169:2516–2523.
75.
Rodriguez-Jimenez FJ, Krause A, Schulz S, Forssmann WG, Conejo-Garcia JR, Schreeb R, Motzkus D: Distribution of new human beta-defensin genes clustered on chromosome 20 in functionally different segments of epididymis. Genomics 2003;81:175–183.
76.
Malm J, Sorensen O, Persson T, Frohm-Nilsson M, Johansson B, Bjartell A, Lilja H, Stahle-Backdahl M, Borregaard N, Egesten A: The human cationic antimicrobial protein (hCAP-18) is expressed in the epithelium of human epididymis, is present in seminal plasma at high concentrations, and is attached to spermatozoa. Infect Immun 2000;68:4297–4302.
77.
Palladino MA, Mallonga TA, Mishra MS: Messenger RNA (mRNA) expression for the antimicrobial peptides beta-defensin-1 and beta-defensin-2 in the male rat reproductive tract: beta-defensin-1 mRNA in initial segment and caput epididymidis is regulated by androgens and not bacterial lipopolysaccharides. Biol Reprod 2003;68:509–515.
78.
Cao D, Li Y, Yang R, Wang Y, Zhou Y, Diao H, Zhao Y, Zhang Y, Lu J: Lipopolysaccharide-induced epididymitis disrupts epididymal beta-defensin expression and inhibits sperm motility in rats. Biol Reprod 2010;83:1064–1070.
79.
Zhou CX, Zhang YL, Xiao L, Zheng M, Leung KM, Chan MY, Lo PS, Tsang LL, Wong HY, Ho LS, Chung YW, Chan HC: An epididymis-specific beta-defensin is important for the initiation of sperm maturation. Nat Cell Biol 2004;6:458–464.
80.
Xu W, Zhang X, Chen W, Fok KL, Rowlands DK, Chui YL, Chan HC: Immunization with Bin1b decreases sperm motility with compromised fertility in rats. Fertil Steril 2010;93:952–958.
81.
Tollner TL, Venners SA, Hollox EJ, Yudin AI, Liu X, Tang G, Xing H, Kays RJ, Lau T, Overstreet JW, Xu X, Bevins CL, Cherr GN: A common mutation in the defensin DEFB126 causes impaired sperm function and subfertility. Sci Transl Med 2011;3:92ra65.
82.
Tollner TL, Yudin AI, Tarantal AF, Treece CA, Overstreet JW, Cherr GN: Beta-defensin 126 on the surface of macaque sperm mediates attachment of sperm to oviductal epithelia. Biol Reprod 2008;78:400–412.
83.
Tollner TL, Yudin AI, Treece CA, Overstreet JW, Cherr GN: Macaque sperm coating protein DEFB126 facilitates sperm penetration of cervical mucus. Hum Reprod 2008;23:2523–2534.
84.
Yudin AI, Treece CA, Tollner TL, Overstreet JW, Cherr GN: The carbohydrate structure of DEFB126, the major component of the cynomolgus Macaque sperm plasma membrane glycocalyx. J Membr Biol 2005;207:119–129.
85.
Yudin AI, Generao SE, Tollner TL, Treece CA, Overstreet JW, Cherr GN: Beta-defensin 126 on the cell surface protects sperm from immunorecognition and binding of anti-sperm antibodies. Biol Reprod 2005;73:1243–1252.
86.
Yudin AI, Tollner TL, Treece CA, Kays R, Cherr GN, Overstreet JW, Bevins CL: Beta-defensin 22 is a major component of the mouse sperm glycocalyx. Reproduction 2008;136:753–765.
87.
Okuda S, Tsutsui H, Shiina K, Sprunck S, Takeuchi H, Yui R, Kasahara RD, Hamamura Y, Mizukami A, Susaki D, Kawano N, Sakakibara T, Namiki S, Itoh K, Otsuka K, Matsuzaki M, Nozaki H, Kuroiwa T, Nakano A, Kanaoka MM, Dresselhaus T, Sasaki N, Higashiyama T: Defensin-like polypeptide LUREs are pollen tube attractants secreted from synergid cells. Nature 2009;458:357–361.
88.
Stotz HU, Spence B, Wang Y: A defensin from tomato with dual function in defense and development. Plant Mol Biol 2009;71:131–143.
89.
Zou J, Mercier C, Koussounadis A, Secombes C: Discovery of multiple beta-defensin like homologues in teleost fish. Mol Immunol 2007;44:638–647.
90.
Oehlers SH, Flores MV, Chen T, Hall CJ, Crosier KE, Crosier PS: Topographical distribution of antimicrobial genes in the zebrafish intestine. Dev Comp Immunol 2011;35:385–391.
91.
Menke DB, Page DC: Sexually dimorphic gene expression in the developing mouse gonad. Gene Expr Patterns 2002;2:359–367.
92.
Richardson L, Venkataraman S, Stevenson P, Yang Y, Burton N, Rao J, Fisher M, Baldock RA, Davidson DR, Christiansen JH: EMAGE mouse embryo spatial gene expression database: 2010 update. Nucleic Acids Res 2010;38:D703–D709.
93.
Anderson KV, Bokla L, Nusslein-Volhard C: Establishment of dorsal-ventral polarity in the Drosophila embryo: the induction of polarity by the Toll gene product. Cell 1985;42:791–798.
94.
Lemaitre B, Nicolas E, Michaut L, Reichhart JM, Hoffmann JA: The dorsoventral regulatory gene cassette spätzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell 1996;86:973–983.
95.
Donald CD, Sun CQ, Lim SD, Macoska J, Cohen C, Amin MB, Young AN, Ganz TA, Marshall FF, Petros JA: Cancer-specific loss of beta-defensin 1 in renal and prostatic carcinomas. Lab Invest 2003;83:501–505.
96.
Gambichler T, Skrygan M, Huyn J, Bechara FG, Sand M, Altmeyer P, Kreuter A: Pattern of mRNA expression of beta-defensins in basal cell carcinoma. BMC Cancer 2006;6:163.
97.
Joly S, Compton LM, Pujol C, Kurago ZB, Guthmiller JM: Loss of human beta-defensin 1, 2, and 3 expression in oral squamous cell carcinoma. Oral Microbiol Immunol 2009;24:353–360.
98.
Schuetz AN, Yin-Goen Q, Amin MB, Moreno CS, Cohen C, Hornsby CD, Yang WL, Petros JA, Issa MM, Pattaras JG, Ogan K, Marshall FF, Young AN: Molecular classification of renal tumors by gene expression profiling. J Mol Diagn 2005;7:206–218.
99.
Arimura Y, Ashitani J, Yanagi S, Tokojima M, Abe K, Mukae H, Nakazato M: Elevated serum beta-defensins concentrations in patients with lung cancer. Anticancer Res 2004;24:4051–4057.
100.
Kesting MR, Loeffelbein DJ, Hasler RJ, Wolff KD, Rittig A, Schulte M, Hirsch T, Wagenpfeil S, Jacobsen F, Steinstraesser L: Expression profile of human beta-defensin 3 in oral squamous cell carcinoma. Cancer Invest 2009;27:575–581.
101.
Liu SY, Chang LC, Pan LF, Hung YJ, Lee CH, Shieh YS: Clinicopathologic significance of tumor cell-lined vessel and microenvironment in oral squamous cell carcinoma. Oral Oncol 2008;44:277–285.
102.
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;45:696–702.
103.
Winter J, Pantelis A, Reich R, Martini M, Kraus D, Jepsen S, Allam JP, Novak N, Wenghoefer M: Human beta-defensin-1, -2, and -3 exhibit opposite effects on oral squamous cell carcinoma cell proliferation. Cancer Invest 2011;29:196–201.
104.
Bullard RS, Gibson W, Bose SK, Belgrave JK, Eaddy AC, Wright CJ, Hazen-Martin DJ, Lage JM, Keane TE, Ganz TA, Donald CD: Functional analysis of the host defense peptide human beta defensin-1: new insight into its potential role in cancer. Mol Immunol 2008;45:839–848.
© 2012 S. Karger AG, Basel
2012
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.