Expression of PPARc and Paraoxonase 2 Correlated with Pseudomonas aeruginosa Infection in Cystic Fibrosis

The Pseudomonas aeruginosa quorum sensing signal molecule N-3-oxododecanoyl-L-homoserine lactone (3OC12HSL) can inhibit function of the mammalian anti-inflammatory transcription factor peroxisome proliferator activated receptor (PPAR)c, and can be degraded by human paraoxonase (PON)2. Because 3OC12HSL is detected in lungs of cystic fibrosis (CF) patients infected with P. aeruginosa, we investigated the relationship between P. aeruginosa infection and gene expression of PPARc and PON2 in bronchoalveolar lavage fluid (BALF) of children with CF. Total RNA was extracted from cell pellets of BALF from 43 children aged 6 months–5 years and analyzed by reverse transcription–quantitative real time PCR for gene expression of PPARc, PON2, and P. aeruginosa lasI, the 3OC12HSL synthase. Patients with culture-confirmed P. aeruginosa infection had significantly lower gene expression of PPARc and PON2 than patients without P. aeruginosa infection. All samples that were culture-positive for P. aeruginosa were also positive for lasI expression. There was no significant difference in PPARc or PON2 expression between patients without culture-detectable infection and those with non-Pseudomonal bacterial infection, so reduced expression was specifically associated with P. aeruginosa infection. Expression of both PPARc and PON2 was inversely correlated with neutrophil counts in BALF, but showed no correlation with other variables evaluated. Thus, lower PPARc and PON2 gene expression in the BALF of children with CF is associated specifically with P. aeruginosa infection and neutrophilia. We cannot differentiate whether this is a cause or the effect of P. aeruginos