This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Suzuki, M.
Right arrow Articles by Podolsky, D. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Suzuki, M.
Right arrow Articles by Podolsky, D. K.

 Previous Article  |  Next Article 

Infection and Immunity, June 2003, p. 3503-3511, Vol. 71, No. 6
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.6.3503-3511.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Gamma Interferon Augments the Intracellular Pathway for Lipopolysaccharide (LPS) Recognition in Human Intestinal Epithelial Cells through Coordinated Up-Regulation of LPS Uptake and Expression of the Intracellular Toll-Like Receptor 4-MD-2 Complex

Manabu Suzuki, Tadakazu Hisamatsu, and Daniel K. Podolsky*

Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts

Received 10 September 2002/ Returned for modification 5 November 2002/ Accepted 6 February 2003

Although some intestinal epithelial cell lines are known to respond to lipopolysaccharide (LPS), understanding of the relationship between LPS responsiveness and the expression of LPS receptors or factors regulating LPS responsiveness of intestinal epithelial cell lines is incomplete. In this study, we demonstrate that commonly studied human intestinal epithelial cell lines can be classified into at least three different types on the basis of LPS responsiveness, Toll-like receptor-4 (TLR4) expression, and the effects of gamma interferon (IFN-{gamma}) on LPS responsiveness. The first phenotype, which includes the HCT-116 and Caco-2 cell lines, is characterized by relative hyporesponsiveness to LPS and diminished expression of TLR4 protein. In these cells, IFN-{gamma} does not induce LPS responsiveness. The second phenotype, which includes cell line SW480, exhibits a highly LPS-responsive phenotype and surface expression of TLR4 protein even in unprimed conditions. These lines are functionally similar to cells of monocytic lineage. In the third phenotype, which includes the HT-29 and Colo205 cell lines, TLR4 protein is largely present in the cytoplasmic fraction and the cells are hyporesponsive to LPS in an unprimed condition. However, priming of these cells with IFN-{gamma} can induce LPS responsiveness through augmentation of LPS uptake and expression of MD-2 mRNA and intracellular TLR4 proteins. Finally, these findings suggest that the Th1 cytokine IFN-{gamma} modulates LPS responsiveness through several mechanisms in intestinal epithelial cells and that these cells may comprise different subpopulations with distinct roles in innate immune responses.

* Corresponding author. Mailing address: Gastrointestinal Unit, Massachusetts General Hospital, 32 Fruit St., Boston, MA 02114. Phone: (617) 726-7411. Fax: (617) 724-2136. E-mail: Podolsky.Daniel{at}mgh.harvard.edu.

Editor: W. A. Petri, Jr.

Infection and Immunity, June 2003, p. 3503-3511, Vol. 71, No. 6
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.6.3503-3511.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Ohkusa, T., Yoshida, T., Sato, N., Watanabe, S., Tajiri, H., Okayasu, I. (2009). Commensal bacteria can enter colonic epithelial cells and induce proinflammatory cytokine secretion: a possible pathogenic mechanism of ulcerative colitis. J Med Microbiol 58: 535-545 [Abstract] [Full Text]  
  • Abolhassani, M., Aloulou, N., Chaumette, M. T., Aparicio, T., Martin-Garcia, N., Mansour, H., Le Gouvello, S., Delchier, J. C., Sobhani, I. (2008). Leptin Receptor-Related Immune Response in Colorectal Tumors: The Role of Colonocytes and Interleukin-8. Cancer Res. 68: 9423-9432 [Abstract] [Full Text]  
  • Han, S., Wang, G., Qi, X., Englander, E. W., Greeley, G. H. Jr. (2008). Involvement of a Stat3 binding site in inflammation-induced enteric apelin expression. Am. J. Physiol. Gastrointest. Liver Physiol. 295: G1068-G1078 [Abstract] [Full Text]  
  • Canny, G. O., McCormick, B. A. (2008). Bacteria in the Intestine, Helpful Residents or Enemies from Within?. Infect. Immun. 76: 3360-3373 [Full Text]  
  • Gribar, S. C., Anand, R. J., Sodhi, C. P., Hackam, D. J. (2008). The role of epithelial Toll-like receptor signaling in the pathogenesis of intestinal inflammation. J. Leukoc. Biol. 83: 493-498 [Abstract] [Full Text]  
  • Leaphart, C. L., Cavallo, J., Gribar, S. C., Cetin, S., Li, J., Branca, M. F., Dubowski, T. D., Sodhi, C. P., Hackam, D. J. (2007). A Critical Role for TLR4 in the Pathogenesis of Necrotizing Enterocolitis by Modulating Intestinal Injury and Repair. J. Immunol. 179: 4808-4820 [Abstract] [Full Text]  
  • Bogunovic, M., Dave, S. H., Tilstra, J. S., Chang, D. T. W., Harpaz, N., Xiong, H., Mayer, L. F., Plevy, S. E. (2007). Enteroendocrine cells express functional Toll-like receptors. Am. J. Physiol. Gastrointest. Liver Physiol. 292: G1770-G1783 [Abstract] [Full Text]  
  • Palazzo, M., Balsari, A., Rossini, A., Selleri, S., Calcaterra, C., Gariboldi, S., Zanobbio, L., Arnaboldi, F., Shirai, Y. F., Serrao, G., Rumio, C. (2007). Activation of Enteroendocrine Cells via TLRs Induces Hormone, Chemokine, and Defensin Secretion. J. Immunol. 178: 4296-4303 [Abstract] [Full Text]  
  • Visintin, A., Halmen, K. A., Khan, N., Monks, B. G., Golenbock, D. T., Lien, E. (2006). MD-2 expression is not required for cell surface targeting of Toll-like receptor 4 (TLR4). J. Leukoc. Biol. 80: 1584-1592 [Abstract] [Full Text]  
  • Jilling, T., Simon, D., Lu, J., Meng, F. J., Li, D., Schy, R., Thomson, R. B., Soliman, A., Arditi, M., Caplan, M. S. (2006). The Roles of Bacteria and TLR4 in Rat and Murine Models of Necrotizing Enterocolitis.. J. Immunol. 177: 3273-3282 [Abstract] [Full Text]  
  • Mueller, T., Terada, T., Rosenberg, I. M., Shibolet, O., Podolsky, D. K. (2006). Th2 Cytokines Down-Regulate TLR Expression and Function in Human Intestinal Epithelial Cells. J. Immunol. 176: 5805-5814 [Abstract] [Full Text]  
  • Gatti, G., Rivero, V., Motrich, R. D., Maccioni, M. (2006). Prostate epithelial cells can act as early sensors of infection by up-regulating TLR4 expression and proinflammatory mediators upon LPS stimulation. J. Leukoc. Biol. 79: 989-998 [Abstract] [Full Text]  
  • Yu, F.-S. X., Hazlett, L. D. (2006). Toll-like Receptors and the Eye.. IOVS 47: 1255-1263 [Full Text]  
  • Cario, E., Golenbock, D. T., Visintin, A., Runzi, M., Gerken, G., Podolsky, D. K. (2006). Trypsin-Sensitive Modulation of Intestinal Epithelial MD-2 as Mechanism of Lipopolysaccharide Tolerance. J. Immunol. 176: 4258-4266 [Abstract] [Full Text]  
  • Neal, M. D., Leaphart, C., Levy, R., Prince, J., Billiar, T. R., Watkins, S., Li, J., Cetin, S., Ford, H., Schreiber, A., Hackam, D. J. (2006). Enterocyte TLR4 Mediates Phagocytosis and Translocation of Bacteria Across the Intestinal Barrier.. J. Immunol. 176: 3070-3079 [Abstract] [Full Text]  
  • Canny, G., Cario, E., Lennartsson, A., Gullberg, U., Brennan, C., Levy, O., Colgan, S. P. (2006). Functional and biochemical characterization of epithelial bactericidal/permeability-increasing protein. Am. J. Physiol. Gastrointest. Liver Physiol. 290: G557-G567 [Abstract] [Full Text]  
  • Ortega-Cava, C. F., Ishihara, S., Rumi, M. A. K., Aziz, M. M., Kazumori, H., Yuki, T., Mishima, Y., Moriyama, I., Kadota, C., Oshima, N., Amano, Y., Kadowaki, Y., Ishimura, N., Kinoshita, Y. (2006). Epithelial Toll-Like Receptor 5 Is Constitutively Localized in the Mouse Cecum and Exhibits Distinctive Down-Regulation during Experimental Colitis. CVI 13: 132-138 [Abstract] [Full Text]  
  • Gomariz, R. P., Arranz, A., Abad, C., Torroba, M., Martinez, C., Rosignoli, F., Garcia-Gomez, M., Leceta, J., Juarranz, Y. (2005). Time-course expression of Toll-like receptors 2 and 4 in inflammatory bowel disease and homeostatic effect of VIP. J. Leukoc. Biol. 78: 491-502 [Abstract] [Full Text]  
  • Cario, E (2005). BACTERIAL INTERACTIONS WITH CELLS OF THE INTESTINAL MUCOSA: TOLL-LIKE RECEPTORS AND NOD2. Gut 54: 1182-1193 [Full Text]  
  • Schiffrin, E. J., Yousfi, M. E., Faure, M., Combaret, L., Donnet, A., Blum, S., Obled, C., Breuille, D. (2005). Milk Casein-Based Diet Containing TGF-{beta} Controls the Inflammatory Reaction in the HLA-B27 Transgenic Rat Model. JPEN J Parenter Enteral Nutr 29: S141-S150 [Abstract] [Full Text]  
  • Fukata, M., Michelsen, K. S., Eri, R., Thomas, L. S., Hu, B., Lukasek, K., Nast, C. C., Lechago, J., Xu, R., Naiki, Y., Soliman, A., Arditi, M., Abreu, M. T. (2005). Toll-like receptor-4 is required for intestinal response to epithelial injury and limiting bacterial translocation in a murine model of acute colitis. Am. J. Physiol. Gastrointest. Liver Physiol. 288: G1055-G1065 [Abstract] [Full Text]  
  • Abreu, M. T., Fukata, M., Arditi, M. (2005). TLR Signaling in the Gut in Health and Disease. J. Immunol. 174: 4453-4460 [Abstract] [Full Text]  
  • Servin, A. L. (2005). Pathogenesis of Afa/Dr Diffusely Adhering Escherichia coli. Clin. Microbiol. Rev. 18: 264-292 [Abstract] [Full Text]  
  • Vora, P., Youdim, A., Thomas, L. S., Fukata, M., Tesfay, S. Y., Lukasek, K., Michelsen, K. S., Wada, A., Hirayama, T., Arditi, M., Abreu, M. T. (2004). {beta}-Defensin-2 Expression Is Regulated by TLR Signaling in Intestinal Epithelial Cells. J. Immunol. 173: 5398-5405 [Abstract] [Full Text]  
  • Dunzendorfer, S., Lee, H.-K., Soldau, K., Tobias, P. S. (2004). TLR4 Is the Signaling but Not the Lipopolysaccharide Uptake Receptor. J. Immunol. 173: 1166-1170 [Abstract] [Full Text]  
  • Cetin, S., Ford, H. R., Sysko, L. R., Agarwal, C., Wang, J., Neal, M. D., Baty, C., Apodaca, G., Hackam, D. J. (2004). Endotoxin Inhibits Intestinal Epithelial Restitution through Activation of Rho-GTPase and Increased Focal Adhesions. J. Biol. Chem. 279: 24592-24600 [Abstract] [Full Text]  
  • Chang, J. H., McCluskey, P., Wakefield, D. (2004). Expression of Toll-like Receptor 4 and Its Associated Lipopolysaccharide Receptor Complex by Resident Antigen-Presenting Cells in the Human Uvea. IOVS 45: 1871-1878 [Abstract] [Full Text]  
  • Kim, J. G., Lee, S. J., Kagnoff, M. F. (2004). Nod1 Is an Essential Signal Transducer in Intestinal Epithelial Cells Infected with Bacteria That Avoid Recognition by Toll-Like Receptors. Infect. Immun. 72: 1487-1495 [Abstract] [Full Text]  
  • Monick, M. M., Yarovinsky, T. O., Powers, L. S., Butler, N. S., Carter, A. B., Gudmundsson, G., Hunninghake, G. W. (2003). Respiratory Syncytial Virus Up-regulates TLR4 and Sensitizes Airway Epithelial Cells to Endotoxin. J. Biol. Chem. 278: 53035-53044 [Abstract] [Full Text]  
  • Hisamatsu, T., Suzuki, M., Podolsky, D. K. (2003). Interferon-{gamma} Augments CARD4/NOD1 Gene and Protein Expression through Interferon Regulatory Factor-1 in Intestinal Epithelial Cells. J. Biol. Chem. 278: 32962-32968 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»