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 Moors, M. A.
Right arrow Articles by Mizel, S. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Moors, M. A.
Right arrow Articles by Mizel, S. B.

 Previous Article  |  Next Article 

Infection and Immunity, July 2001, p. 4424-4429, Vol. 69, No. 7
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.7.4424-4429.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Activation of Interleukin-1 Receptor-Associated Kinase by Gram-Negative Flagellin

Marlena A. Moors,1 Liwu Li,2 and Steven B. Mizel1,*

Department of Microbiology and Immunology1 and Section of Infectious Diseases, Department of Internal Medicine,2 Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157

Received 25 January 2001/Accepted 2 April 2001

Flagellin from various species of gram-negative bacteria activates monocytes to produce proinflammatory cytokines. We have analyzed the pathway by which Salmonella enteritidis flagellin (FliC) activates murine and human monocyte/macrophage-like cell lines. Since lipopolysaccharide (LPS), the principal immune stimulatory component of gram-negative bacteria, is known to signal through Toll-like receptor 4 (TLR4), we tested the possibility that FliC also signals via TLR4. When murine HeNC2 cells were stimulated with LPS in the presence of a neutralizing anti-TLR4 monoclonal antibody, tumor necrosis factor alpha (TNF-alpha ) and nitric oxide (NO) production were markedly reduced. In contrast, FliC-mediated TNF-alpha and NO production were minimally affected by the anti-TLR4 antibody. Furthermore, FliC, unlike LPS, stimulated TNF-alpha production in the TLR4 mutant cell line, GG2EE, indicating that TLR4 is not essential for FliC-mediated signaling. To test the possibility that FliC signals via another TLR, we measured FliC-mediated activation of interleukin-1 (IL-1) receptor-associated kinase (IRAK), a central component in IL-1R/TLR signaling. FliC induced IRAK activation in HeNC2 and GG2EE cells as well as in the human promonocytic cell line THP-1. IRAK activation was rapid in HeNC2 cells, with maximal activity observed after 5 min of treatment with FliC. In addition, FliC-mediated IRAK activation exhibited the same concentration dependence as was demonstrated for the induction of TNF-alpha . These results represent the first demonstration of IRAK activation by a purified bacterial protein and strongly suggest that a TLR distinct from TLR4 is involved in the macrophage inflammatory response to FliC.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Wake Forest University School of Medicine, Winston-Salem, NC 27157. Phone: (336) 716-2216. Fax: (336) 716-9928. E-mail: smizel{at}wfubmc.edu.

Infection and Immunity, July 2001, p. 4424-4429, Vol. 69, No. 7
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.7.4424-4429.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Wang, B.-Z., Quan, F.-S., Kang, S.-M., Bozja, J., Skountzou, I., Compans, R. W. (2008). Incorporation of Membrane-Anchored Flagellin into Influenza Virus-Like Particles Enhances the Breadth of Immune Responses. J. Virol. 82: 11813-11823 [Abstract] [Full Text]  
  • Kato, K., Lu, W., Kai, H., Kim, K. C. (2007). Phosphoinositide 3-kinase is activated by MUC1 but not responsible for MUC1-induced suppression of Toll-like receptor 5 signaling. Am. J. Physiol. Lung Cell. Mol. Physiol. 293: L686-L692 [Abstract] [Full Text]  
  • Ivison, S. M., Graham, N. R., Bernales, C. Q., Kifayet, A., Ng, N., Shobab, L. A., Steiner, T. S. (2007). Protein Kinase D Interaction with TLR5 Is Required for Inflammatory Signaling in Response to Bacterial Flagellin. J. Immunol. 178: 5735-5743 [Abstract] [Full Text]  
  • Sun, J., Fegan, P. E., Desai, A. S., Madara, J. L., Hobert, M. E. (2007). Flagellin-induced tolerance of the Toll-like receptor 5 signaling pathway in polarized intestinal epithelial cells. Am. J. Physiol. Gastrointest. Liver Physiol. 292: G767-G778 [Abstract] [Full Text]  
  • Lu, W., Hisatsune, A., Koga, T., Kato, K., Kuwahara, I., Lillehoj, E. P., Chen, W., Cross, A. S., Gendler, S. J., Gewirtz, A. T., Kim, K. C. (2006). Cutting Edge: Enhanced Pulmonary Clearance of Pseudomonas aeruginosa by Muc1 Knockout Mice. J. Immunol. 176: 3890-3894 [Abstract] [Full Text]  
  • Verma, A., Arora, S. K., Kuravi, S. K., Ramphal, R. (2005). Roles of Specific Amino Acids in the N Terminus of Pseudomonas aeruginosa Flagellin and of Flagellin Glycosylation in the Innate Immune Response. Infect. Immun. 73: 8237-8246 [Abstract] [Full Text]  
  • Wright, K. J., Seed, P. C., Hultgren, S. J. (2005). Uropathogenic Escherichia coli Flagella Aid in Efficient Urinary Tract Colonization. Infect. Immun. 73: 7657-7668 [Abstract] [Full Text]  
  • De Nardo, D., Masendycz, P., Ho, S., Cross, M., Fleetwood, A. J., Reynolds, E. C., Hamilton, J. A., Scholz, G. M. (2005). A Central Role for the Hsp90{middle dot}Cdc37 Molecular Chaperone Module in Interleukin-1 Receptor-associated-kinase-dependent Signaling by Toll-like Receptors. J. Biol. Chem. 280: 9813-9822 [Abstract] [Full Text]  
  • West, A. P., Dancho, B. A., Mizel, S. B. (2005). Gangliosides Inhibit Flagellin Signaling in the Absence of an Effect on Flagellin Binding to Toll-like Receptor 5. J. Biol. Chem. 280: 9482-9488 [Abstract] [Full Text]  
  • Greene, C. M., Carroll, T. P., Smith, S. G. J., Taggart, C. C., Devaney, J., Griffin, S., O'Neill, S. J., McElvaney, N. G. (2005). TLR-Induced Inflammation in Cystic Fibrosis and Non-Cystic Fibrosis Airway Epithelial Cells. J. Immunol. 174: 1638-1646 [Abstract] [Full Text]  
  • Huang, Y., Li, T., Sane, D. C., Li, L. (2004). IRAK1 Serves as a Novel Regulator Essential for Lipopolysaccharide-induced Interleukin-10 Gene Expression. J. Biol. Chem. 279: 51697-51703 [Abstract] [Full Text]  
  • Tsujita, T., Tsukada, H., Nakao, M., Oshiumi, H., Matsumoto, M., Seya, T. (2004). Sensing Bacterial Flagellin by Membrane and Soluble Orthologs of Toll-like Receptor 5 in Rainbow Trout (Onchorhynchus mikiss). J. Biol. Chem. 279: 48588-48597 [Abstract] [Full Text]  
  • Lyons, S., Wang, L., Casanova, J. E., Sitaraman, S. V., Merlin, D., Gewirtz, A. T. (2004). Salmonella typhimurium transcytoses flagellin via an SPI2-mediated vesicular transport pathway. J. Cell Sci. 117: 5771-5780 [Abstract] [Full Text]  
  • Noubir, S., Hmama, Z., Reiner, N. E. (2004). Dual Receptors and Distinct Pathways Mediate Interleukin-1 Receptor-associated Kinase Degradation in Response to Lipopolysaccharide: INVOLVEMENT OF CD14/TLR4, CR3, AND PHOSPHATIDYLINOSITOL 3-KINASE. J. Biol. Chem. 279: 25189-25195 [Abstract] [Full Text]  
  • Didierlaurent, A., Ferrero, I., Otten, L. A., Dubois, B., Reinhardt, M., Carlsen, H., Blomhoff, R., Akira, S., Kraehenbuhl, J.-P., Sirard, J.-C. (2004). Flagellin Promotes Myeloid Differentiation Factor 88-Dependent Development of Th2-Type Response. J. Immunol. 172: 6922-6930 [Abstract] [Full Text]  
  • Adamo, R., Sokol, S., Soong, G., Gomez, M. I., Prince, A. (2004). Pseudomonas aeruginosa Flagella Activate Airway Epithelial Cells through asialoGM1 and Toll-Like Receptor 2 as well as Toll-Like Receptor 5. Am. J. Respir. Cell Mol. Bio. 30: 627-634 [Abstract] [Full Text]  
  • Maaser, C., Heidemann, J., von Eiff, C., Lugering, A., Spahn, T. W., Binion, D. G., Domschke, W., Lugering, N., Kucharzik, T. (2004). Human Intestinal Microvascular Endothelial Cells Express Toll-Like Receptor 5: A Binding Partner for Bacterial Flagellin. J. Immunol. 172: 5056-5062 [Abstract] [Full Text]  
  • Murthy, K. G. K., Deb, A., Goonesekera, S., Szabo, C., Salzman, A. L. (2004). Identification of Conserved Domains in Salmonella muenchen Flagellin That Are Essential for Its Ability to Activate TLR5 and to Induce an Inflammatory Response in Vitro. J. Biol. Chem. 279: 5667-5675 [Abstract] [Full Text]  
  • Yu, Y., Zeng, H., Lyons, S., Carlson, A., Merlin, D., Neish, A. S., Gewirtz, A. T. (2003). TLR5-mediated activation of p38 MAPK regulates epithelial IL-8 expression via posttranscriptional mechanism. Am. J. Physiol. Gastrointest. Liver Physiol. 285: G282-G290 [Abstract] [Full Text]  
  • Mizel, S. B., West, A. P., Hantgan, R. R. (2003). Identification of a Sequence in Human Toll-like Receptor 5 Required for the Binding of Gram-negative Flagellin. J. Biol. Chem. 278: 23624-23629 [Abstract] [Full Text]  
  • Mizel, S. B., Honko, A. N., Moors, M. A., Smith, P. S., West, A. P. (2003). Induction of Macrophage Nitric Oxide Production by Gram-Negative Flagellin Involves Signaling Via Heteromeric Toll-Like Receptor 5/Toll-Like Receptor 4 Complexes. J. Immunol. 170: 6217-6223 [Abstract] [Full Text]  
  • Means, T. K., Hayashi, F., Smith, K. D., Aderem, A., Luster, A. D. (2003). The Toll-Like Receptor 5 Stimulus Bacterial Flagellin Induces Maturation and Chemokine Production in Human Dendritic Cells. J. Immunol. 170: 5165-5175 [Abstract] [Full Text]  
  • Jacinto, R., Hartung, T., McCall, C., Li, L. (2002). Lipopolysaccharide- and Lipoteichoic Acid-Induced Tolerance and Cross-Tolerance: Distinct Alterations in IL-1 Receptor-Associated Kinase. J. Immunol. 168: 6136-6141 [Abstract] [Full Text]  
  • Mizel, S. B., Snipes, J. A. (2002). Gram-negative Flagellin-induced Self-tolerance Is Associated with a Block in Interleukin-1 Receptor-associated Kinase Release from Toll-like Receptor 5. J. Biol. Chem. 277: 22414-22420 [Abstract] [Full Text]  
  • Hu, J., Jacinto, R., McCall, C., Li, L. (2002). Regulation of IL-1 Receptor-Associated Kinases by Lipopolysaccharide. J. Immunol. 168: 3910-3914 [Abstract] [Full Text]  
  • Liaudet, L., Murthy, K. G. K., Mabley, J. G., Pacher, P., Soriano, F. G., Salzman, A. L., Szabo, C. (2002). Comparison of Inflammation, Organ Damage, and Oxidant Stress Induced by Salmonella enterica Serovar Muenchen Flagellin and Serovar Enteritidis Lipopolysaccharide. Infect. Immun. 70: 192-198 [Abstract] [Full Text]  
  • Li, C., Wang, Y., Gao, L., Zhang, J., Shao, J., Wang, S., Feng, W., Wang, X., Li, M., Chang, Z. (2002). Expression of Toll-like Receptors 2 and 4 and CD14 during Differentiation of HL-60 Cells Induced by Phorbol 12-Myristate 13-Acetate and 1{alpha}, 25-Dihydroxy-Vitamin D3. Cell Growth Differ. 13: 27-38 [Abstract] [Full Text]  
  • Walsh, D. E., Greene, C. M., Carroll, T. P., Taggart, C. C., Gallagher, P. M., O'Neill, S. J., McElvaney, N. G. (2001). Interleukin-8 Up-regulation by Neutrophil Elastase Is Mediated by MyD88/IRAK/TRAF-6 in Human Bronchial Epithelium. J. Biol. Chem. 276: 35494-35499 [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»