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Journal of Bacteriology, July 2008, p. 4408-4415, Vol. 190, No. 13
0021-9193/08/$08.00+0     doi:10.1128/JB.01444-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Peroxisome Proliferator-Activated Receptors Mediate Host Cell Proinflammatory Responses to Pseudomonas aeruginosa Autoinducer{triangledown}

Aruna Jahoor,1 Rashila Patel,2 Amanda Bryan,1 Catherine Do,2 Jay Krier,2 Chase Watters,1 Walter Wahli,3 Guigen Li,4 Simon C. Williams,1* and Kendra P. Rumbaugh2*

Departments of Cell Biology and Biochemistry,1 Surgery, Texas Tech University Health Sciences Center, Lubbock, Texas 79430,2 Center for Integrative Genomics and National Research Center Frontiers in Genetics, University of Lausanne, CH-1015 Lausanne, Switzerland,3 Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas 794094

Received 6 September 2007/ Accepted 23 December 2007

The pathogenic bacterium Pseudomonas aeruginosa utilizes the 3-oxododecanoyl homoserine lactone (3OC12-HSL) autoinducer as a signaling molecule to coordinate the expression of virulence genes through quorum sensing. 3OC12-HSL also affects responses in host cells, including the upregulation of genes encoding inflammatory cytokines. This proinflammatory response may exacerbate underlying disease during P. aeruginosa infections. The specific mechanism(s) through which 3OC12-HSL influences host responses is unclear, and no mammalian receptors for 3OC12-HSL have been identified to date. Here, we report that 3OC12-HSL increases mRNA levels for a common panel of proinflammatory genes in murine fibroblasts and human lung epithelial cells. To identify putative 3OC12-HSL receptors, we examined the expression patterns of a panel of nuclear hormone receptors in these two cell lines and determined that both peroxisome proliferator-activated receptor beta/delta (PPARβ/{delta}) and PPAR{gamma} were expressed. 3OC12-HSL functioned as an agonist of PPARβ/{delta} transcriptional activity and an antagonist of PPAR{gamma} transcriptional activity and inhibited the DNA binding ability of PPAR{gamma}. The proinflammatory effect of 3OC12-HSL in lung epithelial cells was blocked by the PPAR{gamma} agonist rosiglitazone, suggesting that 3OC12-HSL and rosiglitazone are mutually antagonistic negative and positive regulators of PPAR{gamma} activity, respectively. These data identify PPARβ/{delta} and PPAR{gamma} as putative mammalian 3OC12-HSL receptors and suggest that PPAR{gamma} agonists may be employed as anti-inflammatory therapeutics for P. aeruginosa infections.

* Corresponding author. Mailing address for Kendra P. Rumbaugh: Department of Surgery, Texas Tech University Health Sciences Center, 3601 4th St., Lubbock, TX 79430. Phone: (806) 743-2460, ext. 264. Fax: (806) 743-2370. E-mail: kendra.rumbaugh{at}ttuhsc.edu. Mailing address for Simon C. Williams: Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, 3601 4th St., Lubbock, TX 79430. Phone: (806) 743-2524. Fax: (806) 743-2990. E-mail: simon.williams{at}ttuhsc.edu

{triangledown} Published ahead of print on 4 January 2008.

Journal of Bacteriology, July 2008, p. 4408-4415, Vol. 190, No. 13
0021-9193/08/$08.00+0     doi:10.1128/JB.01444-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Atkinson, S., Williams, P. (2009). Quorum sensing and social networking in the microbial world. J R Soc Interface 6: 959-978 [Abstract] [Full Text]  
  • von Bodman, S. B., Willey, J. M., Diggle, S. P. (2008). Cell-Cell Communication in Bacteria: United We Stand. J. Bacteriol. 190: 4377-4391 [Full Text]  


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