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*
Laboratory of Mucosal Immunology, Department of Medicine, University of California at San Diego, La Jolla, CA 92093;
Will Rogers Institute Pulmonary Research Laboratory, Department of Medicine, University of California, Los Angeles, CA 90095; and
Magainin Pharmaceuticals Inc., Plymouth Meeting, PA 19462
The intestinal epithelium forms a physical barrier to limit access
of enteric microbes to the host and contributes to innate host defense
by producing effector molecules against luminal microbes. To further
define the role of the intestinal epithelium in antimicrobial host
defense, we analyzed the expression, regulation, and production of two
antimicrobial peptides, human defensins hBD-1 and hBD-2, by human
intestinal epithelial cells in vitro and in vivo. The human colon
epithelial cell lines HT-29 and Caco-2 constitutively express hBD-1
mRNA and protein but not hBD-2. However, hBD-2 expression is rapidly
induced by IL-1
stimulation or infection of those cells with
enteroinvasive bacteria. Moreover, hBD-2 functions as a NF-
B target
gene in the intestinal epithelium as blocking NF-B activation
inhibits the up-regulated expression of hBD-2 in response to IL-1
stimulation or bacterial infection. Caco-2 cells produce two hBD-1
isoforms and a hBD-2 peptide larger in size than previously described
hBD-2 isoforms. Paralleling the in vitro findings, human
fetal intestinal xenografts constitutively express hBD-1, but not
hBD-2, and hBD-2 expression, but not hBD-1, is up-regulated in
xenografts infected intraluminally with Salmonella.
hBD-1 is expressed by the epithelium of normal human colon and small
intestine, with a similar pattern of expression in inflamed colon. In
contrast, there is little hBD-2 expression by the epithelium of normal
colon, but abundant hBD-2 expression by the epithelium of inflamed
colon. hBD-1 and hBD-2 may be integral components of epithelial innate
immunity in the intestine, with each occupying a distinct functional
niche in intestinal mucosal defense.
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M Bajaj-Elliott Trypsin and host defence: a new role for an old enzyme Gut, February 1, 2003; 52(2): 166 - 167. [Full Text] [PDF]
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 A. E. King, D. C. Fleming, H. O.D. Critchley, and R. W. Kelly Regulation of natural antibiotic expression by inflammatory mediators and mimics of infection in human endometrial epithelial cells Mol. Hum. Reprod., April 1, 2002; 8(4): 341 - 349. [Abstract] [Full Text] [PDF]
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 S. SCHALLER-BALS, A. SCHULZE, and R. BALS Increased Levels of Antimicrobial Peptides in Tracheal Aspirates of Newborn Infants during Infection Am. J. Respir. Crit. Care Med., April 1, 2002; 165(7): 992 - 995. [Abstract] [Full Text] [PDF]
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H. S. Kim, J. H. Cho, H. W. Park, H. Yoon, M. S. Kim, and S. C. Kim Endotoxin-Neutralizing Antimicrobial Proteins of the Human Placenta J. Immunol., March 1, 2002; 168(5): 2356 - 2364. [Abstract] [Full Text] [PDF]
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K. Hase, L. Eckmann, J. D. Leopard, N. Varki, and M. F. Kagnoff Cell Differentiation Is a Key Determinant of Cathelicidin LL-37/Human Cationic Antimicrobial Protein 18 Expression by Human Colon Epithelium Infect. Immun., February 1, 2002; 70(2): 953 - 063. [Abstract] [Full Text] [PDF]
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T. G. A. M. Wolfs, W. A. Buurman, A. van Schadewijk, B. de Vries, M. A. R. C. Daemen, P. S. Hiemstra, and C. van 't Veer In Vivo Expression of Toll-Like Receptor 2 and 4 by Renal Epithelial Cells: IFN-{gamma} and TNF-{alpha} Mediated Up-Regulation During Inflammation J. Immunol., February 1, 2002; 168(3): 1286 - 1293. [Abstract] [Full Text] [PDF]
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Y. Tsutsumi-Ishii and I. Nagaoka NF-{kappa}B-mediated transcriptional regulation of human {beta}-defensin-2 gene following lipopolysaccharide stimulation J. Leukoc. Biol., January 1, 2002; 71(1): 154 - 162. [Abstract] [Full Text] [PDF]
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S. Krisanaprakornkit, J. R. Kimball, and B. A. Dale Regulation of Human {beta}-Defensin-2 in Gingival Epithelial Cells: The Involvement of Mitogen-Activated Protein Kinase Pathways, But Not the NF-{kappa}B Transcription Factor Family J. Immunol., January 1, 2002; 168(1): 316 - 324. [Abstract] [Full Text] [PDF]
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N. S. Goncalves, M. Ghaem-Maghami, G. Monteleone, G. Frankel, G. Dougan, D. J. M. Lewis, C. P. Simmons, and T. T. MacDonald Critical Role for Tumor Necrosis Factor Alpha in Controlling the Number of Lumenal Pathogenic Bacteria and Immunopathology in Infectious Colitis Infect. Immun., November 1, 2001; 69(11): 6651 - 6659. [Abstract] [Full Text] [PDF]
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D. Yang, O. Chertov, and J. J. Oppenheim Participation of mammalian defensins and cathelicidins in anti-microbial immunity: receptors and activities of human defensins and cathelicidin (LL-37) J. Leukoc. Biol., May 1, 2001; 69(5): 691 - 697. [Abstract] [Full Text]
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C. Zhao, T. Nguyen, L. Liu, R. E. Sacco, K. A. Brogden, and R. I. Lehrer Gallinacin-3, an Inducible Epithelial {beta}-Defensin in the Chicken Infect. Immun., April 1, 2001; 69(4): 2684 - 2691. [Abstract] [Full Text] [PDF]
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M. Cecilia Berin, L. Eckmann, D. H. Broide, and M. F. Kagnoff Regulated Production of the T Helper 2-Type T-Cell Chemoattractant TARC by Human Bronchial Epithelial Cells In Vitro and in Human Lung Xenografts Am. J. Respir. Cell Mol. Biol., April 1, 2001; 24(4): 382 - 389. [Abstract] [Full Text]
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 A. Izadpanah, M. B. Dwinell, L. Eckmann, N. M. Varki, and M. F. Kagnoff Regulated MIP-3{alpha}/CCL20 production by human intestinal epithelium: mechanism for modulating mucosal immunity Am J Physiol Gastrointest Liver Physiol, April 1, 2001; 280(4): G710 - G719. [Abstract] [Full Text] [PDF]
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 C. M. Steppan, E. J. Brown, C. M. Wright, S. Bhat, R. R. Banerjee, C. Y. Dai, G. H. Enders, D. G. Silberg, X. Wen, G. D. Wu, et al. A family of tissue-specific resistin-like molecules PNAS, January 16, 2001; 98(2): 502 - 506. [Abstract] [Full Text] [PDF]
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V. Kaiser and G. Diamond Expression of mammalian defensin genes J. Leukoc. Biol., December 1, 2000; 68(6): 779 - 784. [Abstract] [Full Text]
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 R. Krzysiek, E. A. Lefevre, J. Bernard, A. Foussat, P. Galanaud, F. Louache, and Y. Richard Regulation of CCR6 chemokine receptor expression and responsiveness to macrophage inflammatory protein-3alpha /CCL20 in human B cells Blood, October 1, 2000; 96(7): 2338 - 2345. [Abstract] [Full Text] [PDF]
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M. G. Scott, C. M. Rosenberger, M. R. Gold, B. B. Finlay, and R. E. W. Hancock An {alpha}-Helical Cationic Antimicrobial Peptide Selectively Modulates Macrophage Responses to Lipopolysaccharide and Directly Alters Macrophage Gene Expression J. Immunol., September 15, 2000; 165(6): 3358 - 3365. [Abstract] [Full Text] [PDF]
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D. A. O'Neil, S. P. Cole, E. Martin-Porter, M. P. Housley, L. Liu, T. Ganz, and M. F. Kagnoff Regulation of Human beta -Defensins by Gastric Epithelial Cells in Response to Infection with Helicobacter pylori or Stimulation with Interleukin-1 Infect. Immun., September 1, 2000; 68(9): 5412 - 5415. [Abstract] [Full Text] [PDF]
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 K.S. Sahasrabudhe, J.R. Kimball, T.H. Morton, A. Weinberg, and B.A. Dale Expression of the Antimicrobial Peptide, Human {beta}-defensin 1, in Duct Cells of Minor Salivary Glands and Detection in Saliva Journal of Dental Research, September 1, 2000; 79(9): 1669 - 1674. [Abstract] [PDF]
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R N CUNLIFFE and Y R MAHIDA Antimicrobial peptides in innate intestinal host defence Gut, July 1, 2000; 47(1): 16 - 17. [Full Text] [PDF]
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J. Krijgsveld, S. A. J. Zaat, J. Meeldijk, P. A. van Veelen, G. Fang, B. Poolman, E. Brandt, J. E. Ehlert, A. J. Kuijpers, G. H. M. Engbers, et al. Thrombocidins, Microbicidal Proteins from Human Blood Platelets, Are C-terminal Deletion Products of CXC Chemokines J. Biol. Chem., June 30, 2000; 275(27): 20374 - 20381. [Abstract] [Full Text] [PDF]
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M. N. Becker, G. Diamond, M. W. Verghese, and S. H. Randell CD14-dependent Lipopolysaccharide-induced beta -Defensin-2 Expression in Human Tracheobronchial Epithelium J. Biol. Chem., September 15, 2000; 275(38): 29731 - 29736. [Abstract] [Full Text] [PDF]
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J. Harder, J. Bartels, E. Christophers, and J.-M. Schroder Isolation and Characterization of Human beta -Defensin-3, a Novel Human Inducible Peptide Antibiotic J. Biol. Chem., February 16, 2001; 276(8): 5707 - 5713. [Abstract] [Full Text] [PDF]
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K.-i. Ogushi, A. Wada, T. Niidome, N. Mori, K. Oishi, T. Nagatake, A. Takahashi, H. Asakura, S.-i. Makino, H. Hojo, et al. Salmonella enteritidis FliC (Flagella Filament Protein) Induces Human beta -Defensin-2 mRNA Production by Caco-2 Cells J. Biol. Chem., August 3, 2001; 276(32): 30521 - 30526. [Abstract] [Full Text] [PDF]
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Y. Yamaguchi, S. Fukuhara, T. Nagase, T. Tomita, S. Hitomi, S. Kimura, H. Kurihara, and Y. Ouchi A Novel Mouse beta -Defensin, mBD-6, Predominantly Expressed in Skeletal Muscle J. Biol. Chem., August 17, 2001; 276(34): 31510 - 31514. [Abstract] [Full Text] [PDF]
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Y. S. Lopez-Boado, C. L. Wilson, and W. C. Parks Regulation of Matrilysin Expression in Airway Epithelial Cells by Pseudomonas aeruginosa Flagellin J. Biol. Chem., October 26, 2001; 276(44): 41417 - 41423. [Abstract] [Full Text] [PDF]
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P. Fehlbaum, M. Rao, M. Zasloff, and G. M. Anderson An essential amino acid induces epithelial beta -defensin expression PNAS, November 7, 2000; 97(23): 12723 - 12728. [Abstract] [Full Text] [PDF]
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