Intest Res.  2014 Jan;12(1):20-33. 10.5217/ir.2014.12.1.20.

Antimicrobial Proteins in Intestine and Inflammatory Bowel Diseases

Affiliations
  • 1Department of Microbiology, Hanyang University College of Medicine, Seoul, Korea. jungmogg@hanyang.ac.kr

Abstract

Mucosal surface of the intestinal tract is continuously exposed to a large number of microorganisms. To manage the substantial microbial exposure, epithelial surfaces produce a diverse arsenal of antimicrobial proteins (AMPs) that directly kill or inhibit the growth of microorganisms. Thus, AMPs are important components of innate immunity in the gut mucosa. They are frequently expressed in response to colonic inflammation and infection. Expression of many AMPs, including human beta-defensin 2-4 and cathelicidin, is induced in response to invasion of pathogens or enteric microbiota into the mucosal barrier. In contrast, some AMPs, including human alpha-defensin 5-6 and human beta-defensin 1, are constitutively expressed without microbial contact or invasion. In addition, specific AMPs are reported to be associated with inflammatory bowel disease (IBD) due to altered expression of AMPs or development of autoantibodies against AMPs. The advanced knowledge for AMPs expression in IBD can lead to its potential use as biomarkers for disease activity. Although the administration of exogenous AMPs as therapeutic strategies against IBD is still at an early stage of development, augmented induction of endogenous AMPs may be another interesting future research direction for the protective and therapeutic purposes. This review discusses new advances in our understanding of how intestinal AMPs protect against pathogens and contribute to pathophysiology of IBD.

Keyword

Antimicrobial protein; Antimicrobial peptide; Colitis; Inflammatory bowel diseases

MeSH Terms

Autoantibodies
Biomarkers
Colitis
Colon
Humans
Immunity, Innate
Inflammation
Inflammatory Bowel Diseases*
Intestines*
Microbiota
Mucous Membrane
Autoantibodies

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Intest Res. 2017;15(1):124-129.    doi: 10.5217/ir.2017.15.1.124.

Epigenetic Alterations in Inflammatory Bowel Disease and Cancer
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Reference

1. Kim JM. Inflammatory bowel diseases and enteric microbiota. Korean J Gastroenterol. 2010; 55:4–18. PMID: 20098062.
Article
2. Johansson ME, Ambort D, Pelaseyed T, et al. Composition and functional role of the mucus layers in the intestine. Cell Mol Life Sci. 2011; 68:3635–3641. PMID: 21947475.
Article
3. Subramani DB, Johansson ME, Dahlen G, Hansson GC. Lactobacillus and Bifidobacterium species do not secrete protease that cleaves the MUC2 mucin which organises the colon mucus. Benef Microbes. 2010; 1:343–350. PMID: 21831773.
Article
4. Vaishnava S, Yamamoto M, Severson KM, et al. The antibacterial lectin RegIIIgamma promotes the spatial segregation of microbiota and host in the intestine. Science. 2011; 334:255–258. PMID: 21998396.
5. Pasupuleti M, Schmidtchen A, Malmsten M. Antimicrobial peptides: key components of the innate immune system. Crit Rev Biotechnol. 2012; 32:143–171. PMID: 22074402.
Article
6. Cederlund A, Gudmundsson GH, Agerberth B. Antimicrobial peptides important in innate immunity. FEBS J. 2011; 278:3942–3951. PMID: 21848912.
Article
7. Kagan BL, Selsted ME, Ganz T, Lehrer RI. Antimicrobial defensin peptides form voltage-dependent ion-permeable channels in planar lipid bilayer membranes. Proc Natl Acad Sci U S A. 1990; 87:210–214. PMID: 1688654.
Article
8. Papo N, Shai Y. Can we predict biological activity of antimicrobial peptides from their interactions with model phospholipid membranes? Peptides. 2003; 24:1693–1703. PMID: 15019200.
Article
9. Sass V, Schneider T, Wilmes M, et al. Human beta-defensin 3 inhibits cell wall biosynthesis in Staphylococci. Infect Immun. 2010; 78:2793–2800. PMID: 20385753.
10. Lehrer RI, Lu W. Alpha-defensins in human innate immunity. Immunol Rev. 2012; 245:84–112. PMID: 22168415.
11. van Es JH, Jay P, Gregorieff A, et al. Wnt signalling induces maturation of Paneth cells in intestinal crypts. Nat Cell Biol. 2005; 7:381–386. PMID: 15778706.
Article
12. Koslowski MJ, Kubler I, Chamaillard M, et al. Genetic variants of Wnt transcription factor TCF-4 (TCF7L2) putative promoter region are associated with small intestinal Crohn's disease. PLoS One. 2009; 4:e4496. PMID: 19221600.
Article
13. Swidsinski A, Weber J, Loening-Baucke V, Hale LP, Lochs H. Spatial organization and composition of the mucosal flora in patients with inflammatory bowel disease. J Clin Microbiol. 2005; 43:3380–3389. PMID: 16000463.
Article
14. Giesemann T, Guttenberg G, Aktories K. Human alpha-defensins inhibit Clostridium difficile toxin B. Gastroenterology. 2008; 134:2049–2058. PMID: 18435932.
15. Shi J, Aono S, Lu W, et al. A novel role for defensins in intestinal homeostasis: regulation of IL-1beta secretion. J Immunol. 2007; 179:1245–1253. PMID: 17617617.
Article
16. Hashimoto S, Uto H, Kanmura S, et al. Human neutrophil peptide-1 aggravates dextran sulfate sodium-induced colitis. Inflamm Bowel Dis. 2012; 18:667–675. PMID: 21928371.
Article
17. Cunliffe RN, Kamal M, Rose FR, James PD, Mahida YR. Expression of antimicrobial neutrophil defensins in epithelial cells of active inflammatory bowel disease mucosa. J Clin Pathol. 2002; 55:298–304. PMID: 11919217.
Article
18. Yamaguchi N, Isomoto H, Mukae H, et al. Concentrations of alpha- and beta-defensins in plasma of patients with inflammatory bowel disease. Inflamm Res. 2009; 58:192–197. PMID: 19184352.
Article
19. Kanmura S, Uto H, Numata M, et al. Human neutrophil peptides 1-3 are useful biomarkers in patients with active ulcerative colitis. Inflamm Bowel Dis. 2009; 15:909–917. PMID: 19107772.
20. Ericksen B, Wu Z, Lu W, Lehrer RI. Antibacterial activity and specificity of the six human {alpha}-defensins. Antimicrob Agents Chemother. 2005; 49:269–275. PMID: 15616305.
Article
21. Shen B, Porter EM, Reynoso E, et al. Human defensin 5 expression in intestinal metaplasia of the upper gastrointestinal tract. J Clin Pathol. 2005; 58:687–694. PMID: 15976333.
Article
22. Ishikawa C, Tanabe H, Maemoto A, et al. Precursor processing of human defensin-5 is essential to the multiple functions in vitro and in vivo. J Innate Immun. 2010; 2:66–76. PMID: 20375624.
Article
23. 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. PMID: 12660734.
Article
24. Wehkamp J, Salzman NH, Porter E, et al. Reduced Paneth cell alpha-defensins in ileal Crohn's disease. Proc Natl Acad Sci U S A. 2005; 102:18129–18134. PMID: 16330776.
25. Elphick D, Liddell S, Mahida YR. Impaired luminal processing of human defensin-5 in Crohn's disease: persistence in a complex with chymotrypsinogen and trypsin. Am J Pathol. 2008; 172:702–713. PMID: 18258845.
26. Wehkamp J, Harder J, Weichenthal M, et al. NOD2 (CARD15) mutations in Crohn's disease are associated with diminished mucosal alpha-defensin expression. Gut. 2004; 53:1658–1664. PMID: 15479689.
27. Simms LA, Doecke JD, Walsh MD, Huang N, Fowler EV, Radford-Smith GL. Reduced alpha-defensin expression is associated with inflammation and not NOD2 mutation status in ileal Crohn's disease. Gut. 2008; 57:903–910. PMID: 18305068.
28. Cunliffe RN, Rose FR, Keyte J, Abberley L, Chan WC, Mahida YR. Human defensin 5 is stored in precursor form in normal Paneth cells and is expressed by some villous epithelial cells and by metaplastic Paneth cells in the colon in inflammatory bowel disease. Gut. 2001; 48:176–185. PMID: 11156637.
29. Fahlgren A, Hammarstrom S, Danielsson A, Hammarstrom ML. Increased expression of antimicrobial peptides and lysozyme in colonic epithelial cells of patients with ulcerative colitis. Clin Exp Immunol. 2003; 131:90–101. PMID: 12519391.
Article
30. Ho S, Pothoulakis C, Koon HW. Antimicrobial peptides and colitis. Curr Pharm Des. 2013; 19:40–47. PMID: 22950497.
31. Ouellette AJ, Satchell DP, Hsieh MM, Hagen SJ, Selsted ME. Characterization of luminal paneth cell alpha-defensins in mouse small intestine. Attenuated antimicrobial activities of peptides with truncated amino termini. J Biol Chem. 2000; 275:33969–33973. PMID: 10942762.
32. Masuda K, Sakai N, Nakamura K, Yoshioka S, Ayabe T. Bactericidal activity of mouse alpha-defensin cryptdin-4 predominantly affects noncommensal bacteria. J Innate Immun. 2011; 3:315–326. PMID: 21099205.
33. Yoon YM, Lee JY, Yoo D, et al. Bacteroides fragilis enterotoxin induces human beta-defensin-2 expression in intestinal epithelial cells via a mitogen-activated protein kinase/I kappaB kinase/NF-kappaB-dependent pathway. Infect Immun. 2010; 78:2024–2033. PMID: 20231411.
34. Peyrin-Biroulet L, Beisner J, Wang G, et al. Peroxisome proliferator-activated receptor gamma activation is required for maintenance of innate antimicrobial immunity in the colon. Proc Natl Acad Sci U S A. 2010; 107:8772–8777. PMID: 20421464.
35. Schroeder BO, Wu Z, Nuding S, et al. Reduction of disulphide bonds unmasks potent antimicrobial activity of human beta-defensin 1. Nature. 2011; 469:419–423. PMID: 21248850.
36. Maurice MM, Nakamura H, Gringhuis S, et al. Expression of the thioredoxin-thioredoxin reductase system in the inflamed joints of patients with rheumatoid arthritis. Arthritis Rheum. 1999; 42:2430–2439. PMID: 10555039.
37. Möndel M, Schroeder BO, Zimmermann K, et al. Probiotic E. coli treatment mediates antimicrobial human beta-defensin synthesis and fecal excretion in humans. Mucosal Immunol. 2009; 2:166–172. PMID: 19129752.
38. Wehkamp J, Harder J, Wehkamp K, et al. NF-kappaB- and AP-1-mediated induction of human beta defensin-2 in intestinal epithelial cells by Escherichia coli Nissle 1917: a novel effect of a probiotic bacterium. Infect Immun. 2004; 72:5750–5758. PMID: 15385474.
39. Gaffen SL. Structure and signalling in the IL-17 receptor family. Nat Rev Immunol. 2009; 9:556–567. PMID: 19575028.
40. Ganz T. Defensins: antimicrobial peptides of innate immunity. Nat Rev Immunol. 2003; 3:710–720. PMID: 12949495.
41. Wehkamp J, Fellermann K, Herrlinger KR, et al. Human beta-defensin 2 but not beta-defensin 1 is expressed preferentially in colonic mucosa of inflammatory bowel disease. Eur J Gastroenterol Hepatol. 2002; 14:745–752. PMID: 12169983.
42. Fahlgren A, Hammarstrom S, Danielsson A, Hammarstrom ML. beta-Defensin-3 and -4 in intestinal epithelial cells display increased mRNA expression in ulcerative colitis. Clin Exp Immunol. 2004; 137:379–385. PMID: 15270856.
43. Rahman A, Fahlgren A, Sundstedt C, Hammarstrom S, Danielsson A, Hammarstrom ML. Chronic colitis induces expression of beta-defensins in murine intestinal epithelial cells. Clin Exp Immunol. 2011; 163:123–130. PMID: 21039426.
44. Tollin M, Bergman P, Svenberg T, Jornvall H, Gudmundsson GH, Agerberth B. Antimicrobial peptides in the first line defence of human colon mucosa. Peptides. 2003; 24:523–530. PMID: 12860195.
45. Wehkamp J, Harder J, Weichenthal M, et al. Inducible and constitutive beta-defensins are differentially expressed in Crohn's disease and ulcerative colitis. Inflamm Bowel Dis. 2003; 9:215–223. PMID: 12902844.
46. Aldhous MC, Noble CL, Satsangi J. Dysregulation of human beta-defensin-2 protein in inflammatory bowel disease. PLoS One. 2009; 4:e6285. PMID: 19617917.
47. Nuding S, Fellermann K, Wehkamp J, Stange EF. Reduced mucosal antimicrobial activity in Crohn's disease of the colon. Gut. 2007; 56:1240–1247. PMID: 17456510.
48. Fellermann K, Stange DE, Schaeffeler E, et al. A chromosome 8 gene-cluster polymorphism with low human beta-defensin 2 gene copy number predisposes to Crohn disease of the colon. Am J Hum Genet. 2006; 79:439–448. PMID: 16909382.
49. Bentley RW, Pearson J, Gearry RB, et al. Association of higher DEFB4 genomic copy number with Crohn's disease. Am J Gastroenterol. 2010; 105:354–359. PMID: 19809410.
50. Selsted ME. Theta-defensins: cyclic antimicrobial peptides produced by binary ligation of truncated alpha-defensins. Curr Protein Pept Sci. 2004; 5:365–371. PMID: 15544531.
51. Penberthy WT, Chari S, Cole AL, Cole AM. Retrocyclins and their activity against HIV-1. Cell Mol Life Sci. 2011; 68:2231–2242. PMID: 21553001.
52. Arnett E, Lehrer RI, Pratikhya P, Lu W, Seveau S. Defensins enable macrophages to inhibit the intracellular proliferation of Listeria monocytogenes. Cell Microbiol. 2011; 13:635–651. PMID: 21143570.
53. Bals R, Wilson JM. Cathelicidins-a family of multifunctional antimicrobial peptides. Cell Mol Life Sci. 2003; 60:711–720. PMID: 12785718.
54. Sochacki KA, Barns KJ, Bucki R, Weisshaar JC. Real-time attack on single Escherichia coli cells by the human antimicrobial peptide LL-37. Proc Natl Acad Sci U S A. 2011; 108:E77–E81. PMID: 21464330.
55. Murakami M, Dorschner RA, Stern LJ, Lin KH, Gallo RL. Expression and secretion of cathelicidin antimicrobial peptides in murine mammary glands and human milk. Pediatr Res. 2005; 57:10–15. PMID: 15531744.
56. Schauber J, Iffland K, Frisch S, et al. Histone-deacetylase inhibitors induce the cathelicidin LL-37 in gastrointestinal cells. Mol Immunol. 2004; 41:847–854. PMID: 15261456.
57. Termén S, Tollin M, Rodriguez E, et al. PU.1 and bacterial metabolites regulate the human gene CAMP encoding antimicrobial peptide LL-37 in colon epithelial cells. Mol Immunol. 2008; 45:3947–3955. PMID: 18657865.
58. Schauber J, Rieger D, Weiler F, et al. Heterogeneous expression of human cathelicidin hCAP18/LL-37 in inflammatory bowel diseases. Eur J Gastroenterol Hepatol. 2006; 18:615–621. PMID: 16702850.
59. Koon HW, Shih DQ, Chen J, et al. Cathelicidin signaling via the Toll-like receptor protects against colitis in mice. Gastroenterology. 2011; 141:1852–1863.e3. PMID: 21762664.
60. Tai EK, Wong HP, Lam EK, et al. Cathelicidin stimulates colonic mucus synthesis by up-regulating MUC1 and MUC2 expression through a mitogen-activated protein kinase pathway. J Cell Biochem. 2008; 104:251–258. PMID: 18059019.
61. Otte JM, Zdebik AE, Brand S, et al. Effects of the cathelicidin LL-37 on intestinal epithelial barrier integrity. Regul Pept. 2009; 156:104–117. PMID: 19328825.
62. Raqib R, Sarker P, Bergman P, et al. Improved outcome in shigellosis associated with butyrate induction of an endogenous peptide antibiotic. Proc Natl Acad Sci U S A. 2006; 103:9178–9183. PMID: 16740661.
63. Sarker P, Ahmed S, Tiash S, et al. Phenylbutyrate counteracts Shigella mediated downregulation of cathelicidin in rabbit lung and intestinal epithelia: a potential therapeutic strategy. PLoS One. 2011; 6:e20637. PMID: 21673991.
64. Cobo ER, He C, Hirata K, et al. Entamoeba histolytica induces intestinal cathelicidins but is resistant to cathelicidin-mediated killing. Infect Immun. 2012; 80:143–149. PMID: 22083705.
65. Alam SR, Newby DE, Henriksen PA. Role of the endogenous elastase inhibitor, elafin, in cardiovascular injury: from epithelium to endothelium. Biochem Pharmacol. 2012; 83:695–704. PMID: 22100985.
66. Scott A, Weldon S, Taggart CC. SLPI and elafin: multifunctional antiproteases of the WFDC family. Biochem Soc Trans. 2011; 39:1437–1440. PMID: 21936829.
67. Si-Tahar M, Merlin D, Sitaraman S, Madara JL. Constitutive and regulated secretion of secretory leukocyte proteinase inhibitor by human intestinal epithelial cells. Gastroenterology. 2000; 118:1061–1071. PMID: 10833481.
68. Flach CF, Eriksson A, Jennische E, Lange S, Gunnerek C, Lonnroth I. Detection of elafin as a candidate biomarker for ulcerative colitis by whole-genome microarray screening. Inflamm Bowel Dis. 2006; 12:837–842. PMID: 16954802.
69. Schmid M, Fellermann K, Fritz P, Wiedow O, Stange EF, Wehkamp J. Attenuated induction of epithelial and leukocyte serine antiproteases elafin and secretory leukocyte protease inhibitor in Crohn's disease. J Leukoc Biol. 2007; 81:907–915. PMID: 17200145.
70. Motta JP, Magne L, Descamps D, et al. Modifying the protease, antiprotease pattern by elafin overexpression protects mice from colitis. Gastroenterology. 2011; 140:1272–1282. PMID: 21199654.
71. Reardon C, Lechmann M, Brustle A, et al. Thymic stromal lymphopoetin-induced expression of the endogenous inhibitory enzyme SLPI mediates recovery from colonic inflammation. Immunity. 2011; 35:223–235. PMID: 21820333.
72. Balakrishnan A, Marathe SA, Joglekar M, Chakravortty D. Bactericidal/permeability increasing protein: a multifaceted protein with functions beyond LPS neutralization. Innate Immun. 2013; 19:339–347. PMID: 23160386.
73. Akin H, Tahan G, Ture F, et al. Association between bactericidal/permeability increasing protein (BPI) gene polymorphism (Lys216Glu) and inflammatory bowel disease. J Crohns Colitis. 2011; 5:14–18. PMID: 21272798.
74. Haapamäki MM, Haggblom JO, Gronroos JM, Pekkala E, Alanen K, Nevalainen TJ. Bactericidal/permeability-increasing protein in colonic mucosa in ulcerative colitis. Hepatogastroenterology. 1999; 46:2273–2277. PMID: 10521980.
75. Canny G, Cario E, Lennartsson A, et al. Functional and biochemical characterization of epithelial bactericidal/permeability-increasing protein. Am J Physiol Gastrointest Liver Physiol. 2006; 290:G557–G567. PMID: 16282362.
76. Schultz H. From infection to autoimmunity: a new model for induction of ANCA against the bactericidal/permeability increasing protein (BPI). Autoimmun Rev. 2007; 6:223–227. PMID: 17317612.
77. Schinke S, Fellermann K, Herlyn K, et al. Autoantibodies against the bactericidal/permeability-increasing protein from inflammatory bowel disease patients can impair the antibiotic activity of bactericidal/permeability-increasing protein. Inflamm Bowel Dis. 2004; 10:763–770. PMID: 15626895.
78. Cash HL, Whitham CV, Behrendt CL, Hooper LV. Symbiotic bacteria direct expression of an intestinal bactericidal lectin. Science. 2006; 313:1126–1130. PMID: 16931762.
79. Hervieu V, Christa L, Gouysse G, et al. HIP/PAP, a member of the reg family, is expressed in glucagon-producing enteropancreatic endocrine cells and tumors. Hum Pathol. 2006; 37:1066–1075. PMID: 16867870.
80. Yuk JM, Jo EK. Toll-like receptors and innate immunity. J Bacteriol Virol. 2011; 41:225–235.
81. Hong S, Park S, Yu JW. Pyrin domain (PYD)-containing inflammasome in innate immunity. J Bacteriol Virol. 2011; 41:133–146.
82. Kim SP, Lee GW, Kim CM, Shin SH. Coordinate regulation of Vibrio vulnificus heme receptor hupA expression by cyclic AMP-receptor protein and ferric uptake regulator. J Bacteriol Virol. 2012; 42:294–304.
83. Drago-Serrano ME, de la Garza-Amaya M, Luna JS, Campos-Rodriguez R. Lactoferrin-lipopolysaccharide (LPS) binding as key to antibacterial and antiendotoxic effects. Int Immunopharmacol. 2012; 12:1–9. PMID: 22101278.
84. Kim JM. Roles of enteric microbial composition and metabolism in health and diseases. Korean J Gastroenterol. 2013; 62:191–205. PMID: 24162706.
85. Sidhu R, Wilson P, Wright A, et al. Faecal lactoferrin--a novel test to differentiate between the irritable and inflamed bowel? Aliment Pharmacol Ther. 2010; 31:1365–1370. PMID: 20331581.
86. Abraham BP, Kane S. Fecal markers: calprotectin and lactoferrin. Gastroenterol Clin North Am. 2012; 41:483–495. PMID: 22500530.
87. LaSala PR, Ekhmimi T, Hill AK, Farooqi I, Perrotta PL. Quantitative fecal lactoferrin in toxin-positive and toxin-negative Clostridium difficile specimens. J Clin Microbiol. 2013; 51:311–313. PMID: 23135940.
88. Togawa J, Nagase H, Tanaka K, et al. Oral administration of lactoferrin reduces colitis in rats via modulation of the immune system and correction of cytokine imbalance. J Gastroenterol Hepatol. 2002; 17:1291–1298. PMID: 12423274.
89. Togawa J, Nagase H, Tanaka K, et al. Lactoferrin reduces colitis in rats via modulation of the immune system and correction of cytokine imbalance. Am J Physiol Gastrointest Liver Physiol. 2002; 283:G187–G195. PMID: 12065306.
90. López-Soto F, Leon-Sicairos N, Nazmi K, Bolscher JG, de la Garza M. Microbicidal effect of the lactoferrin peptides lactoferricin17-30, lactoferrampin265-284, and lactoferrin chimera on the parasite Entamoeba histolytica. Biometals. 2010; 23:563–568. PMID: 20140481.
91. Fuqua BK, Vulpe CD, Anderson GJ. Intestinal iron absorption. J Trace Elem Med Biol. 2012; 26:115–119. PMID: 22575541.
92. Ganz T. Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation. Blood. 2003; 102:783–788. PMID: 12663437.
93. Drakesmith H, Prentice AM. Hepcidin and the iron-infection axis. Science. 2012; 338:768–772. PMID: 23139325.
94. Oustamanolakis P, Koutroubakis IE, Messaritakis I, Malliaraki N, Sfiridaki A, Kouroumalis EA. Serum hepcidin and prohepcidin concentrations in inflammatory bowel disease. Eur J Gastroenterol Hepatol. 2011; 23:262–268. PMID: 21285884.
95. Wang L, Trebicka E, Fu Y, et al. The bone morphogenetic protein-hepcidin axis as a therapeutic target in inflammatory bowel disease. Inflamm Bowel Dis. 2012; 18:112–119. PMID: 21351217.
96. Miethke M, Skerra A. Neutrophil gelatinase-associated lipocalin expresses antimicrobial activity by interfering with L-norepinephrine-mediated bacterial iron acquisition. Antimicrob Agents Chemother. 2010; 54:1580–1589. PMID: 20086155.
97. Chan YR, Liu JS, Pociask DA, et al. Lipocalin 2 is required for pulmonary host defense against Klebsiella infection. J Immunol. 2009; 182:4947–4956. PMID: 19342674.
98. Fischbach MA, Lin H, Zhou L, et al. The pathogen-associated iroA gene cluster mediates bacterial evasion of lipocalin 2. Proc Natl Acad Sci U S A. 2006; 103:16502–16507. PMID: 17060628.
99. Flo TH, Smith KD, Sato S, et al. Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron. Nature. 2004; 432:917–921. PMID: 15531878.
100. Yoo do Y, Ko SH, Jung J, Kim YJ, Kim JS, Kim JM. Bacteroides fragilis enterotoxin upregulates lipocalin-2 expression in intestinal epithelial cells. Lab Invest. 2013; 93:384–396. PMID: 23381626.
101. Otto BR, Sparrius M, Verweij-van Vught AM, MacLaren DM. Iron-regulated outer membrane protein of Bacteroides fragilis involved in heme uptake. Infect Immun. 1990; 58:3954–3958. PMID: 2254022.
102. Otto BR, Verweij-van Vught AM, MacLaren DM. Transferrins and heme-compounds as iron sources for pathogenic bacteria. Crit Rev Microbiol. 1992; 18:217–233. PMID: 1532495.
Article
103. Sijbrandi R, Den Blaauwen T, Tame JR, Oudega B, Luirink J, Otto BR. Characterization of an iron-regulated alpha-enolase of Bacteroides fragilis. Microbes Infect. 2005; 7:9–18. PMID: 15716066.
104. Gallo RL, Hooper LV. Epithelial antimicrobial defence of the skin and intestine. Nat Rev Immunol. 2012; 12:503–516. PMID: 22728527.
105. Peschel A, Otto M, Jack RW, Kalbacher H, Jung G, Gotz F. Inactivation of the dlt operon in Staphylococcus aureus confers sensitivity to defensins, protegrins, and other antimicrobial peptides. J Biol Chem. 1999; 274:8405–8410. PMID: 10085071.
106. Robey M, O'Connell W, Cianciotto NP. Identification of Legionella pneumophila rcp, a pagP-like gene that confers resistance to cationic antimicrobial peptides and promotes intracellular infection. Infect Immun. 2001; 69:4276–4286. PMID: 11401964.
107. Gunn JS. The Salmonella PmrAB regulon: lipopolysaccharide modifications, antimicrobial peptide resistance and more. Trends Microbiol. 2008; 16:284–290. PMID: 18467098.
108. Peschel A, Collins LV. Staphylococcal resistance to antimicrobial peptides of mammalian and bacterial origin. Peptides. 2001; 22:1651–1659. PMID: 11587793.
109. Kraus D, Peschel A. Staphylococcus aureus evasion of innate antimicrobial defense. Future Microbiol. 2008; 3:437–451. PMID: 18651815.
110. Nelson DC, Garbe J, Collin M. Cysteine proteinase SpeB from Streptococcus pyogenes - a potent modifier of immunologically important host and bacterial proteins. Biol Chem. 2011; 392:1077–1088. PMID: 22050223.
111. Shafer WM, Veal WL, Lee EH, Zarantonelli L, Balthazar JT, Rouquette C. Genetic organization and regulation of antimicrobial efflux systems possessed by Neisseria gonorrhoeae and Neisseria meningitidis. J Mol Microbiol Biotechnol. 2001; 3:219–224. PMID: 11321577.
112. Islam D, Bandholtz L, Nilsson J, et al. Downregulation of bactericidal peptides in enteric infections: a novel immune escape mechanism with bacterial DNA as a potential regulator. Nat Med. 2001; 7:180–185. PMID: 11175848.
Article
113. De Yang , Chen Q, Schmidt AP, et al. 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; 192:1069–1074. PMID: 11015447.
114. Kurosaka K, Chen Q, Yarovinsky F, Oppenheim JJ, Yang D. 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. 2005; 174:6257–6265. PMID: 15879124.
115. Yang D, Biragyn A, Kwak LW, Oppenheim JJ. Mammalian defensins in immunity: more than just microbicidal. Trends Immunol. 2002; 23:291–296. PMID: 12072367.
Article
116. Niyonsaba F, Iwabuchi K, Someya A, et al. A cathelicidin family of human antibacterial peptide LL-37 induces mast cell chemotaxis. Immunology. 2002; 106:20–26. PMID: 11972628.
Article
117. Zanetti M. The role of cathelicidins in the innate host defenses of mammals. Curr Issues Mol Biol. 2005; 7:179–196. PMID: 16053249.
118. 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; 69:691–697. PMID: 11358975.
Article
119. Yang D, Chertov O, Bykovskaia SN, et al. Beta-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6. Science. 1999; 286:525–528. PMID: 10521347.
Article
120. Di Nardo A, Braff MH, Taylor KR, et al. Cathelicidin antimicrobial peptides block dendritic cell TLR4 activation and allergic contact sensitization. J Immunol. 2007; 178:1829–1834. PMID: 17237433.
Article
121. Lande R, Gregorio J, Facchinetti V, et al. Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Nature. 2007; 449:564–569. PMID: 17873860.
Article
122. Hooper LV, Stappenbeck TS, Hong CV, Gordon JI. Angiogenins: a new class of microbicidal proteins involved in innate immunity. Nat Immunol. 2003; 4:269–273. PMID: 12548285.
Article
123. Ménard S, Forster V, Lotz M, et al. Developmental switch of intestinal antimicrobial peptide expression. J Exp Med. 2008; 205:183–193. PMID: 18180308.
Article
124. Iimura M, Gallo RL, Hase K, Miyamoto Y, Eckmann L, Kagnoff MF. Cathelicidin mediates innate intestinal defense against colonization with epithelial adherent bacterial pathogens. J Immunol. 2005; 174:4901–4907. PMID: 15814717.
Article
125. Putsep K, Axelsson LG, Boman A, et al. Germ-free and colonized mice generate the same products from enteric prodefensins. J Biol Chem. 2000; 275:40478–40482. PMID: 11010975.
Article
126. O'Neil DA, Porter EM, Elewaut D, et al. Expression and regulation of the human beta-defensins hBD-1 and hBD-2 in intestinal epithelium. J Immunol. 1999; 163:6718–6724. PMID: 10586069.
127. Hooper LV, Wong MH, Thelin A, Hansson L, Falk PG, Gordon JI. Molecular analysis of commensal host-microbial relationships in the intestine. Science. 2001; 291:881–884. PMID: 11157169.
Article
128. Vaishnava S, Behrendt CL, Ismail AS, Eckmann L, Hooper LV. Paneth cells directly sense gut commensals and maintain homeostasis at the intestinal host-microbial interface. Proc Natl Acad Sci U S A. 2008; 105:20858–20863. PMID: 19075245.
Article
129. Brandl K, Plitas G, Schnabl B, DeMatteo RP, Pamer EG. MyD88-mediated signals induce the bactericidal lectin RegIII gamma and protect mice against intestinal Listeria monocytogenes infection. J Exp Med. 2007; 204:1891–1900. PMID: 17635956.
Article
130. Lim YJ, Jo YH, Kim HJ, Park JK. The synergistic effects of antimicrobial peptides on the growth inhibition of Salmonella Typhimurium through Imd pathway in Drosophila intestine. J Bacteriol Virol. 2013; 43:120–130.
Article
131. Kinnebrew MA, Ubeda C, Zenewicz LA, Smith N, Flavell RA, Pamer EG. Bacterial flagellin stimulates Toll-like receptor 5-dependent defense against vancomycin-resistant Enterococcus infection. J Infect Dis. 2010; 201:534–543. PMID: 20064069.
Article
132. Schauber J, Svanholm C, Termen S, et al. Expression of the cathelicidin LL-37 is modulated by short chain fatty acids in colonocytes: relevance of signalling pathways. Gut. 2003; 52:735–741. PMID: 12692061.
Article
133. Petnicki-Ocwieja T, Hrncir T, Liu YJ, et al. Nod2 is required for the regulation of commensal microbiota in the intestine. Proc Natl Acad Sci U S A. 2009; 106:15813–15818. PMID: 19805227.
Article
134. Wilson CL, Ouellette AJ, Satchell DP, et al. Regulation of intestinal alpha-defensin activation by the metalloproteinase matrilysin in innate host defense. Science. 1999; 286:113–117. PMID: 10506557.
Article
135. Ghosh D, Porter E, Shen B, et al. Paneth cell trypsin is the processing enzyme for human defensin-5. Nat Immunol. 2002; 3:583–590. PMID: 12021776.
Article
136. Mukherjee S, Partch CL, Lehotzky RE, et al. Regulation of C-type lectin antimicrobial activity by a flexible N-terminal prosegment. J Biol Chem. 2009; 284:4881–4888. PMID: 19095652.
Article
137. Sørensen O, Arnljots K, Cowland JB, Bainton DF, Borregaard N. The human antibacterial cathelicidin, hCAP-18, is synthesized in myelocytes and metamyelocytes and localized to specific granules in neutrophils. Blood. 1997; 90:2796–2803. PMID: 9326247.
Article
138. Chu H, Pazgier M, Jung G, et al. Human alpha-defensin 6 promotes mucosal innate immunity through self-assembled peptide nanonets. Science. 2012; 337:477–481. PMID: 22722251.
Article
139. Jäger S, Stange EF, Wehkamp J. Inflammatory bowel disease: an impaired barrier disease. Langenbecks Arch Surg. 2013; 398:1–12. PMID: 23160753.
Article
140. Ayabe T, Satchell DP, Wilson CL, Parks WC, Selsted ME, Ouellette AJ. Secretion of microbicidal alpha-defensins by intestinal Paneth cells in response to bacteria. Nat Immunol. 2000; 1:113–118. PMID: 11248802.
Article
141. Burton MF, Steel PG. The chemistry and biology of LL-37. Nat Prod Rep. 2009; 26:1572–1584. PMID: 19936387.
Article
142. Pathan FK, Venkata DA, Panguluri SK. Recent patents on antimicrobial peptides. Recent Pat DNA Gene Seq. 2010; 4:10–16. PMID: 20218955.
Article
143. Kang JK, Hwang JS, Nam HJ, et al. The insect peptide coprisin prevents Clostridium difficile-mediated acute inflammation and mucosal damage through selective antimicrobial activity. Antimicrob Agents Chemother. 2011; 55:4850–4857. PMID: 21807975.
Article
144. Guskey MT, Tsuji BT. A comparative review of the lipoglycopeptides: oritavancin, dalbavancin, and telavancin. Pharmacotherapy. 2010; 30:80–94. PMID: 20030476.
Article
145. Van Bambeke F. Glycopeptides and glycodepsipeptides in clinical development: a comparative review of their antibacterial spectrum, pharmacokinetics and clinical efficacy. Curr Opin Investig Drugs. 2006; 7:740–749.
146. Weber G, Heilborn JD, Chamorro Jimenez CI, Hammarsjo A, Torma H, Stahle M. Vitamin D induces the antimicrobial protein hCAP18 in human skin. J Invest Dermatol. 2005; 124:1080–1082. PMID: 15854055.
Article
147. Wang TT, Dabbas B, Laperriere D, et al. Direct and indirect induction by 1,25-dihydroxyvitamin D3 of the NOD2/CARD15-defensin beta2 innate immune pathway defective in Crohn disease. J Biol Chem. 2010; 285:2227–2231. PMID: 19948723.
Article
148. Steinmann J, Halldorsson S, Agerberth B, Gudmundsson GH. Phenylbutyrate induces antimicrobial peptide expression. Antimicrob Agents Chemother. 2009; 53:5127–5133. PMID: 19770273.
Article
149. Schlee M, Harder J, Koten B, Stange EF, Wehkamp J, Fellermann K. Probiotic lactobacilli and VSL#3 induce enterocyte beta-defensin 2. Clin Exp Immunol. 2008; 151:528–535. PMID: 18190603.
150. Yi H. Development and application of cell-penetrating peptides. J Bacteriol Virol. 2013; 43:177–185.
Article
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