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

 Previous Article  |  Next Article 

Infection and Immunity, August 2003, p. 4614-4622, Vol. 71, No. 8
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.8.4614-4622.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Pseudomonas aeruginosa Slime Glycolipoprotein Is a Potent Stimulant of Tumor Necrosis Factor Alpha Gene Expression and Activation of Transcription Activators Nuclear Factor B and Activator Protein 1 in Human Monocytes

University of Patras Medical School, Department of Microbiology, Patras 26500, Greece

Received 13 January 2003/ Accepted 23 May 2003

Pseudomonas aeruginosa, an opportunistic pathogen, causes infections associated with a high incidence of morbidity and mortality in immunocompromised hosts. Production of tumor necrosis factor alpha (TNF-), primarily by cells of monocytic lineage, is a crucial event in the course of these infections. During in vivo infections with P. aeruginosa, both lipopolysaccharide (LPS) and extracellular slime glycolipoprotein (GLP) produced by mucoid and nonmucoid strains are released. In the present study, we sought to explore the relative contributions of these two bacterial products to TNF- production by human monocytes. To this end, fresh human monocytes and THP-1 human monocytic cells were stimulated with P. aeruginosa LPS or GLP. GLP was found to be a more potent stimulus for TNF- production (threefold higher) by human monocytes than LPS. Moreover, its effect was comparable to that of viable bacteria. Quantitative mRNA analysis revealed predominantly transcriptional regulation. Electrophoretic mobility shift assays and transfection assays demonstrated activation of NF-B and activator protein 1 (AP-1). NF-B activation by GLP was rapid and followed the same time course as that by viable bacteria, suggesting that bacteria could directly activate NF-B through GLP. Moreover P. aeruginosa GLP induced the formation of AP-1 complex with delayed kinetics compared with NF-B but much more efficiently than the homologous LPS. These results identify GLP as the most important stimulant for TNF- production by human monocytes. Activation of NF-B and AP-1 by P. aeruginosa GLP may be involved not only in TNF- induction but also in many of the inflammatory responses triggered in the course of infection with P. aeruginosa.

Editor: J. D. Clements

This article has been cited by other articles:

• Simitsopoulou, M., Roilides, E., Paliogianni, F., Likartsis, C., Ioannidis, J., Kanellou, K., Walsh, T. J. (2008). Immunomodulatory Effects of Voriconazole on Monocytes Challenged with Aspergillus fumigatus: Differential Role of Toll-Like Receptors. Antimicrob. Agents Chemother. 52: 3301-3306 [Abstract] [Full Text]  
• Simitsopoulou, M., Roilides, E., Likartsis, C., Ioannidis, J., Orfanou, A., Paliogianni, F., Walsh, T. J. (2007). Expression of Immunomodulatory Genes in Human Monocytes Induced by Voriconazole in the Presence of Aspergillus fumigatus. Antimicrob. Agents Chemother. 51: 1048-1054 [Abstract] [Full Text]