The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

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
Right arrow Citation Map
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 arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wang, L.
Right arrow Articles by Sitaraman, S. V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wang, L.
Right arrow Articles by Sitaraman, S. V.
The Journal of Immunology, 2003, 171: 3194-3201.
Copyright © 2003 by The American Association of Immunologists

IL-6 Induces NF-{kappa}B Activation in the Intestinal Epithelia 1

Lixin Wang*, Baljit Walia*, John Evans2,*, Andrew T. Gewirtz{dagger}, Didier Merlin* and Shanthi V. Sitaraman3,*

* Department of Medicine, Division of Digestive Diseases and {dagger} Department of Pathology, Epithelial Pathobiology Unit, Emory University, Atlanta, GA 30322

IL-6 is a potent proinflammatory cytokine that has been shown to play an important role in the pathogenesis of inflammatory bowel disease (IBD). It is classically known to activate gene expression via the STAT-3 pathway. Given the crucial role of IL-6 in the pathogenesis of chronic intestinal inflammation, it is not known whether IL-6 activates NF-{kappa}B, a central mediator of intestinal inflammation. The model intestinal epithelial cell line, Caco2-BBE, was used to study IL-6 signaling and to analyze whether suppressor of cytokine signaling 3 (SOCS-3) proteins play a role in the negative regulation of IL-6 signaling. We show that IL-6 receptors are present in intestinal epithelia in a polarized fashion. Basolateral IL-6 and, to a lesser extent, apical IL-6 induces the activation of the NF-{kappa}B pathway. Basolateral IL-6 stimulation results in a maximal induction of NF-{kappa}B activation and NF-{kappa}B nuclear translocation at 2 h. IL-6 induces polarized expression of ICAM-1, an adhesion molecule shown to be important in the neutrophil-epithelial interactions in IBD. Using various deletion constructs of ICAM-1 promoter, we show that ICAM-1 induction by IL-6 requires the activation of NF-{kappa}B. We also demonstrate that overexpression of SOCS-3, a protein known to inhibit STAT activation in response to IL-6, down-regulates IL-6-induced NF-{kappa}B activation and ICAM-1 expression. In summary, we demonstrate the activation of NF-{kappa}B by IL-6 in intestinal epithelia and the down-regulation of NF-{kappa}B induction by SOCS-3. These data may have mechanistic and therapeutic implications in diseases such as IBD and rheumatoid arthritis in which IL-6 plays an important role in the pathogenesis.




This article has been cited by other articles:


Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
K. L. W. Walton, L. Holt, and R. B. Sartor
Lipopolysaccharide activates innate immune responses in murine intestinal myofibroblasts through multiple signaling pathways
Am J Physiol Gastrointest Liver Physiol, March 1, 2009; 296(3): G601 - G611.
[Abstract] [Full Text] [PDF]

Home page
 J ANIM SCIHome page
T. E. Weber, C. J. Ziemer, and B. J. Kerr
Effects of adding fibrous feedstuffs to the diet of young pigs on growth performance, intestinal cytokines, and circulating acute-phase proteins
J Anim Sci, April 1, 2008; 86(4): 871 - 881.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
V. L. Kolachala, R. Bajaj, L. Wang, Y. Yan, J. D. Ritzenthaler, A. T. Gewirtz, J. Roman, D. Merlin, and S. V. Sitaraman
Epithelial-derived Fibronectin Expression, Signaling, and Function in Intestinal Inflammation
J. Biol. Chem., November 9, 2007; 282(45): 32965 - 32973.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. L. Theiss, T. S. Obertone, D. Merlin, and S. V. Sitaraman
Interleukin-6 Transcriptionally Regulates Prohibitin Expression in Intestinal Epithelial Cells
J. Biol. Chem., April 27, 2007; 282(17): 12804 - 12812.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
L. Wang, S. Srinivasan, A. L. Theiss, D. Merlin, and S. V. Sitaraman
Interleukin-6 Induces Keratin Expression in Intestinal Epithelial Cells: POTENTIAL ROLE OF KERATIN-8 IN INTERLEUKIN-6-INDUCED BARRIER FUNCTION ALTERATIONS
J. Biol. Chem., March 16, 2007; 282(11): 8219 - 8227.
[Abstract] [Full Text] [PDF]

Home page
 Exp. Biol. Med.Home page
D. Bugarski, A. Krstic, S. Mojsilovic, M. Vlaski, M. Petakov, G. Jovcic, N. Stojanovic, and P. Milenkovic
Signaling Pathways Implicated in Hematopoietic Progenitor Cell Proliferation and Differentiation
Experimental Biology and Medicine, January 1, 2007; 232(1): 156 - 163.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
B.-C. Chen, C.-C. Liao, M.-J. Hsu, Y.-T. Liao, C.-C. Lin, J.-R. Sheu, and C.-H. Lin
Peptidoglycan-Induced IL-6 Production in RAW 264.7 Macrophages Is Mediated by Cyclooxygenase-2, PGE2/PGE4 Receptors, Protein Kinase A, I{kappa}B Kinase, and NF-{kappa}B
J. Immunol., July 1, 2006; 177(1): 681 - 693.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
I. Karagiannides, E. Kokkotou, M. Tansky, T. Tchkonia, N. Giorgadze, M. O'Brien, S. E. Leeman, J. L. Kirkland, and C. Pothoulakis
Induction of colitis causes inflammatory responses in fat depots: Evidence for substance P pathways in human mesenteric preadipocytes
PNAS, March 28, 2006; 103(13): 5207 - 5212.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
O. Tabary, H. Corvol, E. Boncoeur, K. Chadelat, C. Fitting, J. M. Cavaillon, A. Clement, and J. Jacquot
Adherence of airway neutrophils and inflammatory response are increased in CF airway epithelial cell-neutrophil interactions
Am J Physiol Lung Cell Mol Physiol, March 1, 2006; 290(3): L588 - L596.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
V. Avadhanula, C. A. Rodriguez, G. C. Ulett, L. O. Bakaletz, and E. E. Adderson
Nontypeable Haemophilus influenzae Adheres to Intercellular Adhesion Molecule 1 (ICAM-1) on Respiratory Epithelial Cells and Upregulates ICAM-1 Expression
Infect. Immun., February 1, 2006; 74(2): 830 - 838.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. I. Gomez, S. H. Sokol, A. B. Muir, G. Soong, J. Bastien, and A. S. Prince
Bacterial Induction of TNF-{alpha} Converting Enzyme Expression and IL-6 Receptor {alpha} Shedding Regulates Airway Inflammatory Signaling
J. Immunol., August 1, 2005; 175(3): 1930 - 1936.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
K. Tsuchiya, I. Kawamura, A. Takahashi, T. Nomura, C. Kohda, and M. Mitsuyama
Listeriolysin O-Induced Membrane Permeation Mediates Persistent Interleukin-6 Production in Caco-2 Cells during Listeria monocytogenes Infection In Vitro
Infect. Immun., July 1, 2005; 73(7): 3869 - 3877.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
S. G. Dixit, B. Zingarelli, D. J. Buckley, A. R. Buckley, and G. M. Pauletti
Nitric oxide mediates increased P-glycoprotein activity in interferon-{gamma}-stimulated human intestinal cells
Am J Physiol Gastrointest Liver Physiol, March 1, 2005; 288(3): G533 - G540.
[Abstract] [Full Text] [PDF]

Home page
 GutHome page
A M Westendorf, M Templin, R Geffers, S Deppenmeier, A D Gruber, M Probst-Kepper, W Hansen, R S Liblau, F Gunzer, D Bruder, et al.
CD4+ T cell mediated intestinal immunity: chronic inflammation versus immune regulation
Gut, January 1, 2005; 54(1): 60 - 69.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 2003 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 2003 by The American Association of Immunologists, Inc. All rights reserved.