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 Hajishengallis, G.
Right arrow Articles by Genco, R. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hajishengallis, G.
Right arrow Articles by Genco, R. J.

 Previous Article  |  Next Article 

Infection and Immunity, December 2002, p. 6658-6664, Vol. 70, No. 12
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.12.6658-6664.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Counteracting Interactions between Lipopolysaccharide Molecules with Differential Activation of Toll-Like Receptors

George Hajishengallis,1* Michael Martin,2 Robert E. Schifferle,1 and Robert J. Genco1

Department of Oral Biology, State University of New York at Buffalo, Buffalo, New York 14214,1 Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 352942

Received 7 June 2002/ Returned for modification 10 July 2002/ Accepted 28 August 2002

We investigated counteracting interactions between the lipopolysaccharides (LPS) from Escherichia coli (Ec-LPS) and Porphyromonas gingivalis (Pg-LPS), which induce cellular activation through Toll-like receptor 4 (TLR4) and TLR2, respectively. We found that Ec-LPS induced tolerance in THP-1 cells to subsequent tumor necrosis factor alpha (TNF-{alpha}) and interleukin 1 beta (IL-1ß) induction by Pg-LPS, though the reverse was not true, and looked for explanatory differential effects on the signal transduction pathway. Cells exposed to Pg-LPS, but not to Ec-LPS, displayed persisting expression of IL-1 receptor-associated kinase without apparent degradation, presumably allowing prolonged relay of downstream signals. Accordingly, cells pretreated with Pg-LPS, but not with Ec-LPS, were effectively activated in response to subsequent exposure to either LPS molecule, as evidenced by assessing nuclear factor (NF)-{kappa}B activity. In fact, Pg-LPS primed THP-1 cells for enhanced NF-{kappa}B activation and TNF-{alpha} release upon restimulation with the same LPS. This was a dose-dependent effect and correlated with upregulation of surface TLR2 expression. Furthermore, we observed inhibition of NF-{kappa}B-dependent transcription in a reporter cell line pretreated with Ec-LPS and restimulated with Pg-LPS (compared to cells pretreated with medium only and restimulated with Pg-LPS), but not when the reverse treatment was made. Although Pg-LPS could not make cells tolerant to subsequent activation by Ec-LPS, Pg-LPS inhibited Ec-LPS-induced TNF-{alpha} and IL-6 release when the two molecules were added simultaneously into THP-1 cell cultures. Pg-LPS also suppressed P. gingivalis FimA protein-induced NF-{kappa}B-dependent transcription in the 3E10/huTLR4 reporter cell line, which does not express TLR2. This rules out competition for common signaling intermediates, suggesting that Pg-LPS may block component(s) of the TLR4 receptor complex. Interactions between TLR2 and TLR4 agonists may be important in the regulation of inflammatory reactions.

* Corresponding author. Mailing address: Department of Oral Biology, 135 Foster Hall, 3435 Main St., SUNY at Buffalo, Buffalo, NY 14214. Phone: (716) 829-3518. Fax: (716) 829-3942. E-mail: gh6{at}acsu.buffalo.edu.

Editor: B. B. Finlay

Infection and Immunity, December 2002, p. 6658-6664, Vol. 70, No. 12
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.12.6658-6664.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Gaffen, S.L., Hajishengallis, G. (2008). A New Inflammatory Cytokine on the Block: Re-thinking Periodontal Disease and the Th1/Th2 Paradigm in the Context of Th17 Cells and IL-17. JDR 87: 817-828 [Abstract] [Full Text]  
  • Bainbridge, B. W., Karimi-Naser, L., Reife, R., Blethen, F., Ernst, R. K., Darveau, R. P. (2008). Acyl Chain Specificity of the Acyltransferases LpxA and LpxD and Substrate Availability Contribute to Lipid A Fatty Acid Heterogeneity in Porphyromonas gingivalis. J. Bacteriol. 190: 4549-4558 [Abstract] [Full Text]  
  • Foster, N., Lea, S. R., Preshaw, P. M., Taylor, J. J. (2007). Pivotal Advance: Vasoactive intestinal peptide inhibits up-regulation of human monocyte TLR2 and TLR4 by LPS and differentiation of monocytes to macrophages. J. Leukoc. Biol. 81: 893-903 [Abstract] [Full Text]  
  • Nemoto, E., Darveau, R.P., Foster, B.L., Nogueira-Filho, G.R., Somerman, M.J. (2006). Regulation of Cementoblast Function by P. gingivalis Lipopolysaccharide via TLR2. JDR 85: 733-738 [Abstract] [Full Text]  
  • Yumoto, H., Chou, H.-H., Takahashi, Y., Davey, M., Gibson, F. C. III, Genco, C. A. (2005). Sensitization of Human Aortic Endothelial Cells to Lipopolysaccharide via Regulation of Toll-Like Receptor 4 by Bacterial Fimbria-Dependent Invasion. Infect. Immun. 73: 8050-8059 [Abstract] [Full Text]  
  • Hajishengallis, G., Ratti, P., Harokopakis, E. (2005). Peptide Mapping of Bacterial Fimbrial Epitopes Interacting with Pattern Recognition Receptors. J. Biol. Chem. 280: 38902-38913 [Abstract] [Full Text]  
  • Coats, S. R., Pham, T.-T. T., Bainbridge, B. W., Reife, R. A., Darveau, R. P. (2005). MD-2 Mediates the Ability of Tetra-Acylated and Penta-Acylated Lipopolysaccharides to Antagonize Escherichia coli Lipopolysaccharide at the TLR4 Signaling Complex. J. Immunol. 175: 4490-4498 [Abstract] [Full Text]  
  • Quintana, F. J., Cohen, I. R. (2005). Heat Shock Proteins as Endogenous Adjuvants in Sterile and Septic Inflammation. J. Immunol. 175: 2777-2782 [Abstract] [Full Text]  
  • Chu, H. W., Jeyaseelan, S., Rino, J. G., Voelker, D. R., Wexler, R. B., Campbell, K., Harbeck, R. J., Martin, R. J. (2005). TLR2 Signaling Is Critical for Mycoplasma pneumoniae-Induced Airway Mucin Expression. J. Immunol. 174: 5713-5719 [Abstract] [Full Text]  
  • Hajishengallis, G., Tapping, R. I., Martin, M. H., Nawar, H., Lyle, E. A., Russell, M. W., Connell, T. D. (2005). Toll-Like Receptor 2 Mediates Cellular Activation by the B Subunits of Type II Heat-Labile Enterotoxins. Infect. Immun. 73: 1343-1349 [Abstract] [Full Text]  
  • Muthukuru, M., Jotwani, R., Cutler, C. W. (2005). Oral Mucosal Endotoxin Tolerance Induction in Chronic Periodontitis. Infect. Immun. 73: 687-694 [Abstract] [Full Text]  
  • Zhou, Q., Desta, T., Fenton, M., Graves, D. T., Amar, S. (2005). Cytokine Profiling of Macrophages Exposed to Porphyromonas gingivalis, Its Lipopolysaccharide, or Its FimA Protein. Infect. Immun. 73: 935-943 [Abstract] [Full Text]  
  • Hajishengallis, G., Nawar, H., Tapping, R. I., Russell, M. W., Connell, T. D. (2004). The Type II Heat-Labile Enterotoxins LT-IIa and LT-IIb and Their Respective B Pentamers Differentially Induce and Regulate Cytokine Production in Human Monocytic Cells. Infect. Immun. 72: 6351-6358 [Abstract] [Full Text]  
  • Walter, C., Zahlten, J., Schmeck, B., Schaudinn, C., Hippenstiel, S., Frisch, E., Hocke, A. C., Pischon, N., Kuramitsu, H. K., Bernimoulin, J.-P., Suttorp, N., Krull, M. (2004). Porphyromonas gingivalis Strain-Dependent Activation of Human Endothelial Cells. Infect. Immun. 72: 5910-5918 [Abstract] [Full Text]  
  • Cohen, N., Morisset, J., Emilie, D. (2004). Induction of Tolerance by Porphyromonas gingivalis on APCs: a Mechanism Implicated in Periodontal Infection. JDR 83: 429-433 [Abstract] [Full Text]  
  • Hajishengallis, G., Genco, R. J. (2004). Downregulation of the DNA-Binding Activity of Nuclear Factor-{kappa}B p65 Subunit in Porphyromonas gingivalis Fimbria-Induced Tolerance. Infect. Immun. 72: 1188-1191 [Abstract] [Full Text]  
  • Coats, S. R., Reife, R. A., Bainbridge, B. W., Pham, T.-T. T., Darveau, R. P. (2003). Porphyromonas gingivalis Lipopolysaccharide Antagonizes Escherichia coli Lipopolysaccharide at Toll-Like Receptor 4 in Human Endothelial Cells. Infect. Immun. 71: 6799-6807 [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»