| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
INFLAMMATION/IMMUNITY/MEDIATORS
1Inflammatory Bowel Disease Center, Division of Gastroenterology, Department of Medicine, and 5Department of Pathology, Mount Sinai School of Medicine, New York, New York; 3Inflammatory Bowel Disease Center, 2Division of Pediatric Infectious Diseases, Department of Pediatrics, Steven Spielberg Pediatric Research Center, Burns and Allen Research Institute, and 4Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, California
Submitted 26 July 2004 ; accepted in final form 24 November 2004
Inflammatory bowel disease (IBD) arises from a dysregulated mucosal immune response to luminal bacteria. Toll-like receptor (TLR)4 recognizes LPS and transduces a proinflammatory signal through the adapter molecule myeloid differentiation marker 88 (MyD88). We hypothesized that TLR4 participates in the innate immune response to luminal bacteria and the development of colitis. TLR4–/– and MyD88–/– mice and littermate controls were given 2.5% dextran sodium sulfate (DSS) for 5 or 7 days followed by a 7-day recovery. Colitis was assessed by weight loss, rectal bleeding, and histopathology. Immunostaining was performed for macrophage markers, chemokine expression, and cell proliferation markers. DSS treatment of TLR4–/– mice was associated with striking reduction in acute inflammatory cells compared with wild-type mice despite similar degrees of epithelial injury. TLR4–/– mice experienced earlier and more severe bleeding than control mice. Similar results were seen with MyD88–/– mice, suggesting that this is the dominant downstream pathway. Mesenteric lymph nodes from TLR4–/– and MyD88–/– mice more frequently grew gram-negative bacteria. Altered neutrophil recruitment was due to diminished macrophage inflammatory protein-2 expression by lamina propria macrophages in TLR4–/– and MyD88–/– mice. The similarity in crypt epithelial damage between TLR4–/– or MyD88–/– and wild-type mice was seen despite decreased epithelial proliferation in knockout mice. TLR4 through the adapter molecule MyD88 is important in intestinal response to injury and in limiting bacterial translocation. Despite the diversity of luminal bacteria, other TLRs do not substitute for the role of TLR4 in this acute colitis model. A defective innate immune response may result in diminished bacterial clearance and ultimately dysregulated response to normal flora.
neutrophil chemotaxis; dextran sodium sulfate; inflammatory bowel disease; innate immunity
This article has been cited by other articles:
|
|
 |
|
  K. Singh, R. Chaturvedi, M. Asim, D. P. Barry, N. D. Lewis, M. P. Vitek, and K. T. Wilson The Apolipoprotein E-mimetic Peptide COG112 Inhibits the Inflammatory Response to Citrobacter rodentium in Colonic Epithelial Cells by Preventing NF-{kappa}B Activation J. Biol. Chem., June 13, 2008; 283(24): 16752 - 16761. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. J. Albert and J. S. Marshall Aging in the absence of TLR2 is associated with reduced IFN-{gamma} responses in the large intestine and increased severity of induced colitis J. Leukoc. Biol., April 1, 2008; 83(4): 833 - 842. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. M. Naugler, K. A. Baer, and M. J. Ropeleski Interleukin-11 antagonizes Fas ligand-mediated apoptosis in IEC-18 intestinal epithelial crypt cells: role of MEK and Akt-dependent signaling Am J Physiol Gastrointest Liver Physiol, March 1, 2008; 294(3): G728 - G737. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C Scarpignato NSAID-induced intestinal damage: are luminal bacteria the therapeutic target? Gut, February 1, 2008; 57(2): 145 - 148. [Full Text] [PDF]
|
|
|
|
 |
|
 R. S. Munford Sensing Gram-Negative Bacterial Lipopolysaccharides: a Human Disease Determinant? Infect. Immun., February 1, 2008; 76(2): 454 - 465. [Full Text] [PDF]
|
|
|
|
 |
|
 C. L. Kien, C. P. Peltier, S. Mandal, J. R. Davie, and R. Blauwiekel Effects of the In Vivo Supply of Butyrate on Histone Acetylation of Cecum in Piglets JPEN J Parenter Enteral Nutr, January 1, 2008; 32(1): 51 - 56. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Brandl, G. Plitas, B. Schnabl, R. P. DeMatteo, and E. G. Pamer MyD88-mediated signals induce the bactericidal lectin RegIII{gamma} and protect mice against intestinal Listeria monocytogenes infection J. Exp. Med., August 6, 2007; 204(8): 1891 - 1900. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Divanovic, A. Trompette, L. K. Petiniot, J. L. Allen, L. M. Flick, Y. Belkaid, R. Madan, J. J. Haky, and C. L. Karp Regulation of TLR4 signaling and the host interface with pathogens and danger: the role of RP105 J. Leukoc. Biol., August 1, 2007; 82(2): 265 - 271. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Rakoff-Nahoum and R. Medzhitov Regulation of Spontaneous Intestinal Tumorigenesis Through the Adaptor Protein MyD88 Science, July 6, 2007; 317(5834): 124 - 127. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M M Heimesaat, A Fischer, H-K Jahn, J Niebergall, M Freudenberg, M Blaut, O Liesenfeld, R R Schumann, U B Gobel, and S Bereswill Exacerbation of murine ileitis by Toll-like receptor 4 mediated sensing of lipopolysaccharide from commensal Escherichia coli Gut, July 1, 2007; 56(7): 941 - 948. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. L. Sigalet, L. E. Wallace, J. J. Holst, G. R. Martin, T. Kaji, H. Tanaka, and K. A. Sharkey Enteric neural pathways mediate the anti-inflammatory actions of glucagon-like peptide 2 Am J Physiol Gastrointest Liver Physiol, July 1, 2007; 293(1): G211 - G221. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Bogunovic, S. H. Dave, J. S. Tilstra, D. T. W. Chang, N. Harpaz, H. Xiong, L. F. Mayer, and S. E. Plevy Enteroendocrine cells express functional Toll-like receptors Am J Physiol Gastrointest Liver Physiol, June 1, 2007; 292(6): G1770 - G1783. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Qualls, A. M. Kaplan, N. van Rooijen, and D. A. Cohen Suppression of experimental colitis by intestinal mononuclear phagocytes J. Leukoc. Biol., October 1, 2006; 80(4): 802 - 815. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. CARIO and D. K PODOLSKY Toll-like receptor signaling and its relevance to intestinal inflammation. Ann. N.Y. Acad. Sci., August 1, 2006; 1072: 332 - 338. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Khan, C. Ma, L. A. Knodler, Y. Valdez, C. M. Rosenberger, W. Deng, B. B. Finlay, and B. A. Vallance Toll-Like Receptor 4 Contributes to Colitis Development but Not to Host Defense during Citrobacter rodentium Infection in Mice. Infect. Immun., May 1, 2006; 74(5): 2522 - 2536. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Lotz, D. Gutle, S. Walther, S. Menard, C. Bogdan, and M. W. Hornef Postnatal acquisition of endotoxin tolerance in intestinal epithelial cells J. Exp. Med., April 17, 2006; 203(4): 973 - 984. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. T. Abreu, M. Fukata, and M. Arditi TLR Signaling in the Gut in Health and Disease J. Immunol., April 15, 2005; 174(8): 4453 - 4460. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
