| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
/Smad Signaling and Fail to Inhibit Proinflammatory Gene Expression in Intestinal Epithelial Cells after the Colonization with Colitogenic Enterococcus faecalis1
* Centre for Nutrition and Food Research, Immunobiology of Nutrition, Technical University of Munich, Freising-Weihenstephan, Germany; and Departments of
Pediatrics and
Medicine, Microbiology, and Immunology, and Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC 27599
Nonpathogenic enteric bacterial species initiate and perpetuate experimental colitis in IL-10 gene-deficient mice (IL-10–/–). Bacteria-specific effects on the epithelium are difficult to dissect due to the complex nature of the gut microflora. We showed that IL-10–/– mice compared with wild-type mice fail to inhibit proinflammatory gene expression in native intestinal epithelial cells (IEC) after the colonization with colitogenic Gram-positive Enterococcus faecalis. Interestingly, proinflammatory gene expression was transient after 1 wk of E. faecalis monoassociation in IEC from wild-type mice, but persisted after 14 wk of bacterial colonization in IL-10–/– mice. Accordingly, wild-type IEC expressed phosphorylated NF-
B subunit RelA (p65) and phosphorylated Smad2 only at day 7 after bacterial colonization, whereas E. faecalis-monoassociated IL-10–/– mice triggered persistent RelA, but no Smad2 phosphorylation in IEC at days 3, 7, 14, and 28. Consistent with the induction of TLR2-mediated RelA phosphorylation and proinflammatory gene expression in E. faecalis-stimulated cell lines, TLR2 protein expression was absent after day 7 from E. faecalis-monoassociated wild-type mice, but persisted in IL-10–/– IEC. Of note, TGF-
1-activated Smad signaling was associated with the loss of TLR2 protein expression and the inhibition of NF-B-dependent gene expression in IEC lines. In conclusion, E. faecalis-monoassociated IL-10–/–, but not wild-type mice lack protective TGF-/Smad signaling and fail to inhibit TLR2-mediated proinflammatory gene expression in the intestinal epithelium, suggesting a critical role for IL-10 and TGF- in maintaining normal epithelial cell homeostasis in the interplay with commensal enteric bacteria.
This article has been cited by other articles:
|
|
 |
|
  E. Louis, C. Libioulle, C. Reenaers, J. Belaiche, and M. Georges Genetics of ulcerative colitis: the come-back of interleukin 10 Gut, September 1, 2009; 58(9): 1173 - 1176. [Full Text] [PDF]
|
|
|
|
 |
|
 P. L. Bollyky, B. A. Falk, S. A. Long, A. Preisinger, K. R. Braun, R. P. Wu, S. P. Evanko, J. H. Buckner, T. N. Wight, and G. T. Nepom CD44 Costimulation Promotes FoxP3+ Regulatory T Cell Persistence and Function via Production of IL-2, IL-10, and TGF-{beta} J. Immunol., August 15, 2009; 183(4): 2232 - 2241. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. B. Larmonier, J. K. Uno, K.-M. Lee, T. Karrasch, D. Laubitz, R. Thurston, M. T. Midura-Kiela, F. K. Ghishan, R. B. Sartor, C. Jobin, et al. Limited effects of dietary curcumin on Th-1 driven colitis in IL-10 deficient mice suggest an IL-10-dependent mechanism of protection Am J Physiol Gastrointest Liver Physiol, November 1, 2008; 295(5): G1079 - G1091. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Hoffmann, E. Rath, G. Holzlwimmer, L. Quintanilla-Martinez, D. Loach, G. Tannock, and D. Haller Lactobacillus reuteri 100-23 Transiently Activates Intestinal Epithelial Cells of Mice That Have a Complex Microbiota during Early Stages of Colonization J. Nutr., September 1, 2008; 138(9): 1684 - 1691. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Flanagan, Z. Modrusan, J. Cornelius, A. Chavali, I. Kasman, L. Komuves, L. Mo, and L. Diehl Intestinal Epithelial Cell Up-Regulation of LY6 Molecules during Colitis Results in Enhanced Chemokine Secretion J. Immunol., March 15, 2008; 180(6): 3874 - 3881. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Poutahidis, K. M. Haigis, V. P. Rao, P. R. Nambiar, C. L. Taylor, Z. Ge, K. Watanabe, A. Davidson, B. H. Horwitz, J. G. Fox, et al. Rapid reversal of interleukin-6-dependent epithelial invasion in a mouse model of microbially induced colon carcinoma Carcinogenesis, December 1, 2007; 28(12): 2614 - 2623. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. G. Haase, A. Klawitter, P. Geyer, and G. B. Baretton Expression of the Immunomodulator IL-10 in Type I Pneumocytes of the Rat: Alterations of IL-10 Expression in Radiation-induced Lung Damage J. Histochem. Cytochem., November 1, 2007; 55(11): 1167 - 1172. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Dambacher, F. Beigel, J. Seiderer, D. Haller, B. Goke, C. J Auernhammer, and S. Brand Interleukin 31 mediates MAP kinase and STAT1/3 activation in intestinal epithelial cells and its expression is upregulated in inflammatory bowel disease Gut, September 1, 2007; 56(9): 1257 - 1265. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Ruiz, A. Braune, G. Holzlwimmer, L. Quintanilla-Fend, and D. Haller Quercetin Inhibits TNF-Induced NF-{kappa}B Transcription Factor Recruitment to Proinflammatory Gene Promoters in Murine Intestinal Epithelial Cells J. Nutr., May 1, 2007; 137(5): 1208 - 1215. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. B. Dalby, D. N. Frank, A. L. St. Amand, A. M. Bendele, and N. R. Pace Culture-independent analysis of indomethacin-induced alterations in the rat gastrointestinal microbiota. Appl. Envir. Microbiol., October 1, 2006; 72(10): 6707 - 6715. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Hamano, A. Asgharpour, S. E. Stroup, T. A. Wynn, E. H. Leiter, and E. Houpt Resistance of C57BL/6 Mice to Amoebiasis Is Mediated by Nonhemopoietic Cells but Requires Hemopoietic IL-10 Production J. Immunol., July 15, 2006; 177(2): 1208 - 1213. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Ruiz and D. Haller Functional Diversity of Flavonoids in the Inhibition of the Proinflammatory NF-{kappa}B, IRF, and Akt Signaling Pathways in Murine Intestinal Epithelial Cells J. Nutr., March 1, 2006; 136(3): 664 - 671. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
