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Lee J, Mo JH, Katakura K, et al. Maintenance of colonic homeostasis by distinctive apical TLR9 signalling in intestinal epithelial cells. Nat Cell Biol 2006; 8:1327-1336. This important paper demonstrates that the DNA-sensing TLR9 has different effects on NF-κB activation and epithelial homeostasis depending on whether apical or basolateral TLR9 is activated.
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Lee J, Mo JH, Katakura K, et al. Maintenance of colonic homeostasis by distinctive apical TLR9 signalling in intestinal epithelial cells. Nat Cell Biol 2006; 8:1327-1336. This important paper demonstrates that the DNA-sensing TLR9 has different effects on NF-κB activation and epithelial homeostasis depending on whether apical or basolateral TLR9 is activated.
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2
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33746882098
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Toll-like receptor 9 agonists promote cellular invasion by increasing matrix metalloproteinase activity
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Merrell MA, Ilvesaro JM, Lehtonen N, et al. Toll-like receptor 9 agonists promote cellular invasion by increasing matrix metalloproteinase activity. Mol Cancer Res 2006; 4:437-447.
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Mol Cancer Res
, vol.4
, pp. 437-447
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Merrell, M.A.1
Ilvesaro, J.M.2
Lehtonen, N.3
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3
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TLR9 is required for the gut-associated lymphoid tissue response following oral infection of Toxoplasma gondii
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Minns LA, Menard LC, Foureau DM, et al. TLR9 is required for the gut-associated lymphoid tissue response following oral infection of Toxoplasma gondii. J Immunol 2006; 176:7589-7897.
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J Immunol
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Minns, L.A.1
Menard, L.C.2
Foureau, D.M.3
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4
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Fukata M, Chen A, Klepper A, et al. Cox-2 is regulated by Toll-like receptor-4 (TLR4) signaling: role in proliferation and apoptosis in the intestine. Gastroenterology 2006; 131:862-877. This paper describes how IECs require expression of both TLR4 and MyD88 in order to activate COX-2, which is necessary for epithelial repair in DSS colitis.
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Fukata M, Chen A, Klepper A, et al. Cox-2 is regulated by Toll-like receptor-4 (TLR4) signaling: role in proliferation and apoptosis in the intestine. Gastroenterology 2006; 131:862-877. This paper describes how IECs require expression of both TLR4 and MyD88 in order to activate COX-2, which is necessary for epithelial repair in DSS colitis.
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5
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33747807305
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The roles of bacteria and TLR4 in rat and murine models of necrotizing enterocolitis
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Jilling T, Simon D, Lu J, et al. The roles of bacteria and TLR4 in rat and murine models of necrotizing enterocolitis. J Immunol 2006; 177:3273-3282.
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J Immunol
, vol.177
, pp. 3273-3282
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Jilling, T.1
Simon, D.2
Lu, J.3
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6
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33646374141
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Toll-like receptor 4 contributes to colitis development but not to host defense during Citrobacter rodentium infection in mice
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Khan MA, Ma C, Knodler LA, et al. Toll-like receptor 4 contributes to colitis development but not to host defense during Citrobacter rodentium infection in mice. Infect Immun 2006; 74:2522-2536.
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Infect Immun
, vol.74
, pp. 2522-2536
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Khan, M.A.1
Ma, C.2
Knodler, L.A.3
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7
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Enterocyte TLR4 mediates phagocytosis and translocation of bacteria across the intestinal barrier
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Neal MD, Leaphart C, Levy R, et al. Enterocyte TLR4 mediates phagocytosis and translocation of bacteria across the intestinal barrier. J Immunol 2006; 176:3070-3079.
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J Immunol
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, pp. 3070-3079
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Neal, M.D.1
Leaphart, C.2
Levy, R.3
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8
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33645843063
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Postnatal acquisition of endotoxin tolerance in intestinal epithelial cells
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This important paper describes how tolerance to LPS is established shortly after birth, and how a stable relationship between the intestine and the gut microbiome develops
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Lotz M, Gutle D, Walther S, et al. Postnatal acquisition of endotoxin tolerance in intestinal epithelial cells. J Exp Med 2006; 203:973-984. This important paper describes how tolerance to LPS is established shortly after birth, and how a stable relationship between the intestine and the gut microbiome develops.
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J Exp Med
, vol.203
, pp. 973-984
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Lotz, M.1
Gutle, D.2
Walther, S.3
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9
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Savidge TC, Newman Pan WH, et al. Lipopolysaccharide-induced human enterocyte tolerance to cytokine-mediated interleukin-8 production may occur independently of TLR-4/MD-2 signaling. Pediatr Res 2006; 59:89-95. This paper provides evidence that LPS promotes tolerance of IECs to interleukin-8 secretion in a TLR4-independent manner, without compromising the host response to pathogenic Salmonella species.
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Savidge TC, Newman PG, Pan WH, et al. Lipopolysaccharide-induced human enterocyte tolerance to cytokine-mediated interleukin-8 production may occur independently of TLR-4/MD-2 signaling. Pediatr Res 2006; 59:89-95. This paper provides evidence that LPS promotes tolerance of IECs to interleukin-8 secretion in a TLR4-independent manner, without compromising the host response to pathogenic Salmonella species.
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10
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34047173496
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Nenci A, Becker C, Wullaert A, et al. Epithelial NEMO links innate immunity to chronic intestinal inflammation. Nature 2007; 446:557-561. This outstanding paper demonstrates that a primary NF-κB signaling defect in IECs disrupts intestinal homeostasis, causing an IBD-like phenotype.
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Nenci A, Becker C, Wullaert A, et al. Epithelial NEMO links innate immunity to chronic intestinal inflammation. Nature 2007; 446:557-561. This outstanding paper demonstrates that a primary NF-κB signaling defect in IECs disrupts intestinal homeostasis, causing an IBD-like phenotype.
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Xiao H, Gulen MF, Qin J, et al. The Toll-interleukin-1 receptor member SIGIRR regulates colonic epithelial homeostasis, inflammation, and tumorigenesis. Immunity 2007; 26:461-475. The absence of single immunoglobulin interleukin-1 receptor-related molecule, a negative regulator of Toll-interleukin-1 receptor signaling, leads to commensal-induced upregulation of proinflammatory gene expression, increased pathology in DSS colitis and increased colitis-associated tumor formation.
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Xiao H, Gulen MF, Qin J, et al. The Toll-interleukin-1 receptor member SIGIRR regulates colonic epithelial homeostasis, inflammation, and tumorigenesis. Immunity 2007; 26:461-475. The absence of single immunoglobulin interleukin-1 receptor-related molecule, a negative regulator of Toll-interleukin-1 receptor signaling, leads to commensal-induced upregulation of proinflammatory gene expression, increased pathology in DSS colitis and increased colitis-associated tumor formation.
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Yamamoto-Furusho JK, Barnich N, Xavier R, et al. Centaurin beta1 down-regulates nucleotide-binding oligomerization domains 1- and 2-dependent NF-kappaB activation. J Biol Chem 2006; 281:36060-36070. The small GTPase protein, centaurin B1, acts as a negative regulator of NOD signaling and downregulates NF-κB activation in IECs, suggesting a key role in innate immunity.
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Yamamoto-Furusho JK, Barnich N, Xavier R, et al. Centaurin beta1 down-regulates nucleotide-binding oligomerization domains 1- and 2-dependent NF-kappaB activation. J Biol Chem 2006; 281:36060-36070. The small GTPase protein, centaurin B1, acts as a negative regulator of NOD signaling and downregulates NF-κB activation in IECs, suggesting a key role in innate immunity.
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13
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Begue B, Dumant C, Bambou JC, et al. Microbial induction of CARD15 expression in intestinal epithelial cells via toll-like receptor 5 triggers an antibacterial response loop. J Cell Physiol 2006; 209:241-252. Expression of a Crohn's disease-associated CARD15/NOD-2 mutation leads to suppressed host-protective responses following exposure to commensal bacterial flagellin.
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Begue B, Dumant C, Bambou JC, et al. Microbial induction of CARD15 expression in intestinal epithelial cells via toll-like receptor 5 triggers an antibacterial response loop. J Cell Physiol 2006; 209:241-252. Expression of a Crohn's disease-associated CARD15/NOD-2 mutation leads to suppressed host-protective responses following exposure to commensal bacterial flagellin.
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TLR5-mediated phosphoinositide 3-kinase activation negatively regulates flagellin-induced proinflammatory gene expression
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Yu Y, Nagai S, Wu H, et al. TLR5-mediated phosphoinositide 3-kinase activation negatively regulates flagellin-induced proinflammatory gene expression. J Immunol 2006; 176:6194-6201.
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(2006)
J Immunol
, vol.176
, pp. 6194-6201
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Yu, Y.1
Nagai, S.2
Wu, H.3
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15
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Role of MyD88 in phosphatidylinositol 3-kinase activation by flagellin/toll-like receptor 5 engagement in colonic epithelial cells
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Rhee SH, Kim H, Moyer MP, Pothoulakis C. Role of MyD88 in phosphatidylinositol 3-kinase activation by flagellin/toll-like receptor 5 engagement in colonic epithelial cells. J Biol Chem 2006; 281:18560-18568.
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J Biol Chem
, vol.281
, pp. 18560-18568
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Rhee, S.H.1
Kim, H.2
Moyer, M.P.3
Pothoulakis, C.4
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Cario E, Gerken G, Podolsky DK. Toll-like receptor 2 controls mucosal inflammation by regulating epithelial barrier function. Gastroenterology 2007; 132:1359-1374. TLR2 activation preserves IEC barrier function in a PI3K and MyD88-dependent manner.
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Cario E, Gerken G, Podolsky DK. Toll-like receptor 2 controls mucosal inflammation by regulating epithelial barrier function. Gastroenterology 2007; 132:1359-1374. TLR2 activation preserves IEC barrier function in a PI3K and MyD88-dependent manner.
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2+-dependent signaling by TLR2
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2+-dependent signaling by TLR2. J Immunol 2006; 177:1330-1337.
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J Immunol
, vol.177
, pp. 1330-1337
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Chun, J.1
Prince, A.2
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Subramanian N, Qadri A. Lysophospholipid sensing triggers secretion of flagellin from pathogenic salmonella. Nat Immunol 2006; 7:583-589. Salmonella synthesize and secrete flagellin de novo after direct sensing of host-produced lysophospholipids.
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Subramanian N, Qadri A. Lysophospholipid sensing triggers secretion of flagellin from pathogenic salmonella. Nat Immunol 2006; 7:583-589. Salmonella synthesize and secrete flagellin de novo after direct sensing of host-produced lysophospholipids.
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Nucleotide-binding oligomerization domain-1 and epidermal growth factor receptor: Critical regulators of beta-defensins during Helicobacter pylori infection
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Boughan PK, Argent RH, Body-Malapel M, et al. Nucleotide-binding oligomerization domain-1 and epidermal growth factor receptor: critical regulators of beta-defensins during Helicobacter pylori infection. J Biol Chem 2006; 281:11637-11648.
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J Biol Chem
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, pp. 11637-11648
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Boughan, P.K.1
Argent, R.H.2
Body-Malapel, M.3
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20
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33748039462
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Cash HL, Whitham CV, Behrendt CL, Hooper LV. Symbiotic bacteria direct expression of an intestinal bactericidal lectin. Science 2006; 313:1126-1130. This excellent article describes how microbial colonization of germ-free mice induces epithelial expression of the RegIIIγ lectin and its role in maintaining host-microbial relationships.
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Cash HL, Whitham CV, Behrendt CL, Hooper LV. Symbiotic bacteria direct expression of an intestinal bactericidal lectin. Science 2006; 313:1126-1130. This excellent article describes how microbial colonization of germ-free mice induces epithelial expression of the RegIIIγ lectin and its role in maintaining host-microbial relationships.
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fMLP induces Hsp27 expression, attenuates NF-κB activation, and confers intestinal epithelial cell protection
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Carlson RM, Vavricka SR, Eloranta JJ, et al. fMLP induces Hsp27 expression, attenuates NF-κB activation, and confers intestinal epithelial cell protection. Am J Physiol Gastrointest Liver Physiol 2006; 292:G1070-G1078.
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Am J Physiol Gastrointest Liver Physiol
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Carlson, R.M.1
Vavricka, S.R.2
Eloranta, J.J.3
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Resta-Lenert S, Barrett KE. Probiotics and commensals reverse TNF-alpha- and IFN-gamma-induced dysfunction in human intestinal epithelial cells. Gastroenterology 2006; 130:731-746. Probiotic and commensal bacteria block cytokine-induced downregulation of ion transporter expression and defects in epithelial barrier properties via effects on mitogen-activated protein kinase and PI3K signaling pathways.
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Resta-Lenert S, Barrett KE. Probiotics and commensals reverse TNF-alpha- and IFN-gamma-induced dysfunction in human intestinal epithelial cells. Gastroenterology 2006; 130:731-746. Probiotic and commensal bacteria block cytokine-induced downregulation of ion transporter expression and defects in epithelial barrier properties via effects on mitogen-activated protein kinase and PI3K signaling pathways.
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Expression of nonclassical class I molecules by intestinal epithelial cells
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Perera L, Shao L, Patel A, et al. Expression of nonclassical class I molecules by intestinal epithelial cells. Inflamm Bowel Dis 2007; 13:298-307.
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Inflamm Bowel Dis
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Perera, L.1
Shao, L.2
Patel, A.3
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Buning J, Hundorfean G, Schmitz M, et al. Antigen targeting to MHC class II-enriched late endosomes in colonic epithelial cells: trafficking of luminal antigens studied in vivo in Crohn's colitis patients. FASEB J 2006; 20:359-361. MHC class II expression is upregulated in Crohn's disease epithelial cells and compartmentalizes luminal antigen into late endosomes.
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Buning J, Hundorfean G, Schmitz M, et al. Antigen targeting to MHC class II-enriched late endosomes in colonic epithelial cells: trafficking of luminal antigens studied in vivo in Crohn's colitis patients. FASEB J 2006; 20:359-361. MHC class II expression is upregulated in Crohn's disease epithelial cells and compartmentalizes luminal antigen into late endosomes.
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Epithelia: Lymphocyte interactions in the gut
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Dahan S, Roth-Walter F, Arnaboldi P, et al. Epithelia: lymphocyte interactions in the gut. Immunol Rev 2007; 215:243-253.
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(2007)
Immunol Rev
, vol.215
, pp. 243-253
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Dahan, S.1
Roth-Walter, F.2
Arnaboldi, P.3
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26
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+ T cell proliferation and anti-CD3 stimulated cytokine production.
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+ T cell proliferation and anti-CD3 stimulated cytokine production.
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27
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Gliadin stimulation of murine macrophage inflammatory gene expression and intestinal permeability are MyD88-dependent: Role of the innate immune response in celiac disease
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Thomas KE, Sapone A, Fasano A, Vogel SN. Gliadin stimulation of murine macrophage inflammatory gene expression and intestinal permeability are MyD88-dependent: role of the innate immune response in celiac disease. J Immunol 2006; 176:2512-2521.
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J Immunol
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Thomas, K.E.1
Sapone, A.2
Fasano, A.3
Vogel, S.N.4
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+ T cell responses to infection with the gut parasite Trichuris.
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+ T cell responses to infection with the gut parasite Trichuris.
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Modulation of dendritic cell phenotype and function in an in vitro model of the intestinal epithelium
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Butler M, Ng CY, van Heel DA, et al. Modulation of dendritic cell phenotype and function in an in vitro model of the intestinal epithelium. Eur J Immunol 2006; 36:864-874.
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Eur J Immunol
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Butler, M.1
Ng, C.Y.2
van Heel, D.A.3
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Zhou R, Wei H, Sun R, et al. NKG2D recognition mediates Toll-like receptor 3 signaling-induced breakdown of epithelial homeostasis in the small intestines of mice. Proc Natl Acad Sci U S A 2007; 104:7512-7515. TLR signaling can break down self-tolerance through induction of abnormal expression of ligands for stimulatory natural killer receptors.
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Zhou R, Wei H, Sun R, et al. NKG2D recognition mediates Toll-like receptor 3 signaling-induced breakdown of epithelial homeostasis in the small intestines of mice. Proc Natl Acad Sci U S A 2007; 104:7512-7515. TLR signaling can break down self-tolerance through induction of abnormal expression of ligands for stimulatory natural killer receptors.
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h1-stimulated TLR function; however, this may impair host intestinal innate immune defense.
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h1-stimulated TLR function; however, this may impair host intestinal innate immune defense.
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Wang F, Schwartz BT, Graham WV, et al. IFN-gamma-induced TNFR2 expression is required for TNF-dependent intestinal epithelial barrier dysfunction. Gastroenterology 2006; 131:1153-1163. Interferon-γ primes intestinal epithelia to respond to TNF by inducing TNF receptor-2 expression, which in turn mediates TNF-induced myosin light chain kinase-dependent IEC barrier dysfunction.
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Wang F, Schwartz BT, Graham WV, et al. IFN-gamma-induced TNFR2 expression is required for TNF-dependent intestinal epithelial barrier dysfunction. Gastroenterology 2006; 131:1153-1163. Interferon-γ primes intestinal epithelia to respond to TNF by inducing TNF receptor-2 expression, which in turn mediates TNF-induced myosin light chain kinase-dependent IEC barrier dysfunction.
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Implication of TNF-related apoptosis-inducing ligand in inflammatory intestinal epithelial lesions
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Begue B, Wajant H, Bambou JC, et al. Implication of TNF-related apoptosis-inducing ligand in inflammatory intestinal epithelial lesions. Gastroenterology 2006; 130:1962-1974.
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Begue, B.1
Wajant, H.2
Bambou, J.C.3
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IL-10 protects mouse intestinal epithelial cells from Fas-induced apoptosis via modulating Fas expression and altering caspase-8 and FLIP expression
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Bharhani MS, Borojevic R, Basak S, et al. IL-10 protects mouse intestinal epithelial cells from Fas-induced apoptosis via modulating Fas expression and altering caspase-8 and FLIP expression. Am J Physiol Gastrointest Liver Physiol 2006; 291:G820-G829.
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Bharhani, M.S.1
Borojevic, R.2
Basak, S.3
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Zeissig S, Burgel N, Gunzel D, et al. Changes in expression and distribution of claudin 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn's disease. Gut 2007; 56:61-72. Upregulation of pore-forming claudin 2 and altered regulation and distribution of claudins 5 and 8 are associated with altered tight junction structure and pronounced barrier dysfunction in mild to moderately active Crohn's disease.
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Zeissig S, Burgel N, Gunzel D, et al. Changes in expression and distribution of claudin 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn's disease. Gut 2007; 56:61-72. Upregulation of pore-forming claudin 2 and altered regulation and distribution of claudins 5 and 8 are associated with altered tight junction structure and pronounced barrier dysfunction in mild to moderately active Crohn's disease.
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Claudin profiling in the mouse during postnatal intestinal development and along the gastrointestinal tract reveals complex expression patterns
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Holmes JL, Van Itallie CM, Rasmussen JE, Anderson JM. Claudin profiling in the mouse during postnatal intestinal development and along the gastrointestinal tract reveals complex expression patterns. Gene Expr Patterns 2006; 6:581-588.
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Gene Expr Patterns
, vol.6
, pp. 581-588
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Holmes, J.L.1
Van Itallie, C.M.2
Rasmussen, J.E.3
Anderson, J.M.4
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Recovery of mucosal barrier function in ischemic porcine ileum and colon is stimulated by a novel agonist of the ClC-2 chloride channel, lubiprostone
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Gastrointest Liver Physiol, Chloride channel activation restores intestinal barrier properties by relocalizing occludin to tight junctions in ischemic intestine
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Moeser AJ, Nighot PK, Engelke KJ, et al. Recovery of mucosal barrier function in ischemic porcine ileum and colon is stimulated by a novel agonist of the ClC-2 chloride channel, lubiprostone. Am J Physiol Gastrointest Liver Physiol 2007; 292:G647-G656. Chloride channel activation restores intestinal barrier properties by relocalizing occludin to tight junctions in ischemic intestine.
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Am J Physiol
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Moeser, A.J.1
Nighot, P.K.2
Engelke, K.J.3
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Ho SB, Dvorak LA, Moor RE, et al. Cysteine-rich domains of muc3 intestinal mucin promote cell migration, inhibit apoptosis, and accelerate wound healing. Gastroenterology 2006; 131:1501-1517. This paper demonstrates how the Muc3 mucin cysteine-rich domain plays an active role in epithelial restitution.
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Ho SB, Dvorak LA, Moor RE, et al. Cysteine-rich domains of muc3 intestinal mucin promote cell migration, inhibit apoptosis, and accelerate wound healing. Gastroenterology 2006; 131:1501-1517. This paper demonstrates how the Muc3 mucin cysteine-rich domain plays an active role in epithelial restitution.
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Yan F, Cao H, Cover TL, et al. Soluble proteins produced by probiotic bacteria regulate intestinal epithelial cell survival and growth. Gastroenterology 2007; 132:562-575. Novel proteins, isolated from the probiotic Lactobacillus rhamnosus activated PI3K signaling, inhibited cytokine-induced epithelial cell apoptosis and promoted cell growth in human and mouse colon epithelial cells and cultured mouse colon explants.
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Yan F, Cao H, Cover TL, et al. Soluble proteins produced by probiotic bacteria regulate intestinal epithelial cell survival and growth. Gastroenterology 2007; 132:562-575. Novel proteins, isolated from the probiotic Lactobacillus rhamnosus activated PI3K signaling, inhibited cytokine-induced epithelial cell apoptosis and promoted cell growth in human and mouse colon epithelial cells and cultured mouse colon explants.
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Gut mucosal homeostasis and cellular mediators after severe thermal trauma and the effect of insulin-like growth factor-I in combination with insulin-like growth factor binding protein-3
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Jeschke MG, Bolder U, Chung DH, et al. Gut mucosal homeostasis and cellular mediators after severe thermal trauma and the effect of insulin-like growth factor-I in combination with insulin-like growth factor binding protein-3. Endocrinology 2007; 148:354-362.
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Jeschke, M.G.1
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Chung, D.H.3
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Heparin-binding epidermal growth factor-like growth factor promotes enterocyte migration and proliferation in neonatal rats with necrotizing enterocolitis
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Feng J, Besner GE. Heparin-binding epidermal growth factor-like growth factor promotes enterocyte migration and proliferation in neonatal rats with necrotizing enterocolitis. J Pediatr Surg 2007; 42:214-220.
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Feng, J.1
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Consequences of direct versus indirect activation of epidermal growth factor receptor in intestinal epithelial cells are dictated by protein-tyrosine phosphatase 1B
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McCole DF, Truong A, Bunz M, Barrett KE. Consequences of direct versus indirect activation of epidermal growth factor receptor in intestinal epithelial cells are dictated by protein-tyrosine phosphatase 1B. J Biol Chem 2007; 282:13303-13315.
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McCole, D.F.1
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Barrett, K.E.4
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p38 kinase regulates epidermal growth factor receptor downregulation and cellular migration
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Frey MR, Dise RS, Edelblum KL, Polk DB. p38 kinase regulates epidermal growth factor receptor downregulation and cellular migration. EMBO J 2006; 25:5683-5692.
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EMBO J
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Frey, M.R.1
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Edelblum, K.L.3
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Wound-induced p38MAPK-dependent histone H3 phosphorylation correlates with increased COX-2 expression in enterocytes
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Karrasch T, Steinbrecher KA, Allard B, et al. Wound-induced p38MAPK-dependent histone H3 phosphorylation correlates with increased COX-2 expression in enterocytes. J Cell Physiol 2006; 207:809-815.
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Karrasch, T.1
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Brown SL, Riehl TE, Walker MR, et al. Myd88-dependent positioning of Ptgs2-expressing stromal cells maintains colonic epithelial proliferation during injury. J Clin Invest 2007; 117:258-269. The combination of injury and Myd88 signaling results in repositioning of a subset of prostaglandin endoperoxide synthase 2-expressing stromal cells from the mesenchyme surrounding the middle and upper crypts to an area surrounding the crypt base.
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Brown SL, Riehl TE, Walker MR, et al. Myd88-dependent positioning of Ptgs2-expressing stromal cells maintains colonic epithelial proliferation during injury. J Clin Invest 2007; 117:258-269. The combination of injury and Myd88 signaling results in repositioning of a subset of prostaglandin endoperoxide synthase 2-expressing stromal cells from the mesenchyme surrounding the middle and upper crypts to an area surrounding the crypt base.
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Restitution of single-cell defects in the mouse colon epithelium differs from that of cultured cells
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Günzel D, Florian P, Richter JF, et al. Restitution of single-cell defects in the mouse colon epithelium differs from that of cultured cells. Am J Physiol Regul Integr Comp Physiol 2006; 290:R1496-R1507.
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