This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow An erratum has been published
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 Zughaier, S. M.
Right arrow Articles by Stephens, D. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zughaier, S. M.
Right arrow Articles by Stephens, D. S.
Right arrowPubmed/NCBI databases
*Gene*GEO Profiles
*HomoloGene*UniGene
*Compound via MeSH
*Substance via MeSH
Hazardous Substances DB
*NITRIC OXIDE

 Previous Article  |  Next Article 

Infection and Immunity, May 2005, p. 2940-2950, Vol. 73, No. 5
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.5.2940-2950.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Differential Induction of the Toll-Like Receptor 4-MyD88-Dependent and -Independent Signaling Pathways by Endotoxins

Susu M. Zughaier,1* Shanta M. Zimmer,1 Anup Datta,4 Russell W. Carlson,4 and David S. Stephens1,2,3

Division of Infectious Diseases, Department of Medicine,1 Department of Microbiology and Immunology, Emory University School of Medicine,2 Laboratories of Microbial Pathogenesis, Department of Veterans Affairs Medical Center, Atlanta,3 Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia4

Received 25 October 2004/ Returned for modification 22 November 2004/ Accepted 17 January 2005

The biological response to endotoxin mediated through the Toll-like receptor 4 (TLR4)-MD-2 receptor complex is directly related to lipid A structure or configuration. Endotoxin structure may also influence activation of the MyD88-dependent and -independent signaling pathways of TLR4. To address this possibility, human macrophage-like cell lines (THP-1, U937, and MM6) or murine macrophage RAW 264.7 cells were stimulated with picomolar concentrations of highly purified endotoxins. Harvested supernatants from previously stimulated cells were also used to stimulate RAW 264.7 or 23ScCr (TLR4-deficient) macrophages (i.e., indirect induction). Neisseria meningitidis lipooligosaccharide (LOS) was a potent direct inducer of the MyD88-dependent pathway molecules tumor necrosis factor alpha (TNF-{alpha}), interleukin-1ß (IL-1ß), monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 3{alpha} (MIP-3{alpha}), and the MyD88-independent molecules beta interferon (IFN-ß), nitric oxide, and IFN-{gamma}-inducible protein 10 (IP-10). Escherichia coli 55:B5 and Vibrio cholerae lipopolysaccharides (LPSs) at the same pmole/ml lipid A concentrations induced comparable levels of TNF-{alpha}, IL-1ß, and MIP-3{alpha}, but significantly less IFN-ß, nitric oxide, and IP-10. In contrast, LPS from Salmonella enterica serovars Minnesota and Typhimurium induced amounts of IFN-ß, nitric oxide, and IP-10 similar to meningococcal LOS but much less TNF-{alpha} and MIP-3{alpha} in time course and dose-response experiments. No MyD88-dependent or -independent response to endotoxin was seen in TLR4-deficient cell lines (C3H/HeJ and 23ScCr) and response was restored in TLR4-MD-2-transfected human embryonic kidney 293 cells. Blocking the MyD88-dependent pathway by DNMyD88 resulted in significant reduction of TNF-{alpha} release but did not influence nitric oxide release. IFN-ß polyclonal antibody and IFN-{alpha}/ß receptor 1 antibody significantly reduced nitric oxide release. N. meningitidis endotoxin was a potent agonist of both the MyD88-dependent and -independent signaling pathways of the TLR4 receptor complex of human macrophages. E. coli 55:B5 and Vibrio cholerae LPS, at the same picomolar lipid A concentrations, selectively induced the MyD88-dependent pathway, while Salmonella LPS activated the MyD88-independent pathway.

* Corresponding author. Mailing address: Division of Infectious Diseases, Emory University School of Medicine, VAMC (I-151), 1670 Clairmont Rd, Atlanta, GA 30033. Phone: (404) 321 6111, ext 7454. Fax: (404) 329 2210. E-mail: szughai{at}emory.edu.

Editor: J. D. Clements

Infection and Immunity, May 2005, p. 2940-2950, Vol. 73, No. 5
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.5.2940-2950.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Novem, V., Shui, G., Wang, D., Bendt, A. K., Sim, S. H., Liu, Y., Thong, T. W., Sivalingam, S. P., Ooi, E. E., Wenk, M. R., Tan, G. (2009). Structural and Biological Diversity of Lipopolysaccharides from Burkholderia pseudomallei and Burkholderia thailandensis. CVI 16: 1420-1428 [Abstract] [Full Text]  
  • Worku, M., Morris, A. (2009). Binding of different forms of lipopolysaccharide and gene expression in bovine blood neutrophils. J DAIRY SCI 92: 3185-3193 [Abstract] [Full Text]  
  • Zimmer, S. M., Liu, J., Clayton, J. L., Stephens, D. S., Snyder, J. P. (2008). Paclitaxel Binding to Human and Murine MD-2. J. Biol. Chem. 283: 27916-27926 [Abstract] [Full Text]  
  • Ovstebo, R., Olstad, O. K., Brusletto, B., Moller, A. S., Aase, A., Haug, K. B. F., Brandtzaeg, P., Kierulf, P. (2008). Identification of Genes Particularly Sensitive to Lipopolysaccharide (LPS) in Human Monocytes Induced by Wild-Type versus LPS-Deficient Neisseria meningitidis Strains. Infect. Immun. 76: 2685-2695 [Abstract] [Full Text]  
  • Bhattacharyya, S., Gill, R., Chen, M. L., Zhang, F., Linhardt, R. J., Dudeja, P. K., Tobacman, J. K. (2008). Toll-like Receptor 4 Mediates Induction of the Bcl10-NF{kappa}B-Interleukin-8 Inflammatory Pathway by Carrageenan in Human Intestinal Epithelial Cells. J. Biol. Chem. 283: 10550-10558 [Abstract] [Full Text]  
  • Munford, R. S. (2008). Sensing Gram-Negative Bacterial Lipopolysaccharides: a Human Disease Determinant?. Infect. Immun. 76: 454-465 [Full Text]  
  • Watanabe, T, Higuchi, K, Kobata, A, Nishio, H, Tanigawa, T, Shiba, M, Tominaga, K, Fujiwara, Y, Oshitani, N, Asahara, T, Nomoto, K, Takeuchi, K, Arakawa, T (2008). Non-steroidal anti-inflammatory drug-induced small intestinal damage is Toll-like receptor 4 dependent. Gut 57: 181-187 [Abstract] [Full Text]  
  • Zughaier, S. M., Lindner, B., Howe, J., Garidel, P., Koch, M. H.J., Brandenburg, K., Stephens, D. S. (2007). Physicochemical characterization and biological activity of lipooligosaccharides and lipid A from Neisseria meningitidis. Innate Immunity 13: 343-357 [Abstract]  
  • Parameswaran, N., Pao, C. S., Leonhard, K. S., Kang, D. S., Kratz, M., Ley, S. C., Benovic, J. L. (2006). Arrestin-2 and G Protein-coupled Receptor Kinase 5 Interact with NF{kappa}B1 p105 and Negatively Regulate Lipopolysaccharide-stimulated ERK1/2 Activation in Macrophages. J. Biol. Chem. 281: 34159-34170 [Abstract] [Full Text]  
  • Fichorova, R. N., Trifonova, R. T., Gilbert, R. O., Costello, C. E., Hayes, G. R., Lucas, J. J., Singh, B. N. (2006). Trichomonas vaginalis Lipophosphoglycan Triggers a Selective Upregulation of Cytokines by Human Female Reproductive Tract Epithelial Cells.. Infect. Immun. 74: 5773-5779 [Abstract] [Full Text]  
  • Burch, L. H., Yang, I. V., Whitehead, G. S., Chao, F. G., Berman, K. G., Schwartz, D. A. (2006). The transcriptional response to lipopolysaccharide reveals a role for interferon-{gamma} in lung neutrophil recruitment. Am. J. Physiol. Lung Cell. Mol. Physiol. 291: L677-L682 [Abstract] [Full Text]  
  • Zager, R. A., Johnson, A. C. M., Lund, S., Hanson, S. (2006). Acute renal failure: determinants and characteristics of the injury-induced hyperinflammatory response. Am. J. Physiol. Renal Physiol. 291: F546-F556 [Abstract] [Full Text]  
  • Plant, L., Wan, H., Jonsson, A.-B. (2006). MyD88-Dependent Signaling Affects the Development of Meningococcal Sepsis by Nonlipooligosaccharide Ligands.. Infect. Immun. 74: 3538-3546 [Abstract] [Full Text]  
  • Reynolds, A., Anderson, E. M., Vermeulen, A., Fedorov, Y., Robinson, K., Leake, D., Karpilow, J., Marshall, W. S., Khvorova, A. (2006). Induction of the interferon response by siRNA is cell type- and duplex length-dependent. RNA 12: 988-993 [Abstract] [Full Text]  
  • Sanchez-Alavez, M., Tabarean, I. V., Behrens, M. M., Bartfai, T. (2006). Ceramide mediates the rapid phase of febrile response to IL-1beta. Proc. Natl. Acad. Sci. USA 103: 2904-2908 [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»