Primary airway epithelial cells from asthmatics, but not subjects with COPD, generate elevated extracellular uric acid levels.

<p>(<b>A</b>) Cell culture supernatant analysis of uric acid levels in un-stimulated primary human airway epithelial cells from healthy age-matched control subjects and asthmatics following 24h of culture. (<b>B</b>) Cell culture supernatant analysis of uric acid levels in un-stimulated primary human airway epithelial cells from healthy age-matched control subjects and those with COPD following 24h of culture. Data represent mean +/- SD, n = 5–8. Significance is represented by *p<0.05 relative to healthy controls.</p

Extracellular uric acid levels from human airway epithelial cells can be attenuated with the XDH inhibitor, allopurinol, and the ABCC4 inhibitor, MK-571.

<p><b>(A)</b> Allopurinol (500 μM) and MK-571 (20 μM) treatment for 24h attenuated un-stimulated production of uric acid from HBEC-6KT, a human airway epithelial cell line derived from a healthy individual. <b>(B)</b> <i>XDH</i> and <b>(C)</b> <i>ABCC4</i> gene expression in HBEC-6KT cells. Data represent mean +/- SD, n = 3. Significance is represented by * = p<0.05 relative to control.</p

Clinical subject characteristics.

<p>Clinical subject characteristics.</p

Extracellular uric acid levels in cultured human airway epithelial cells are not augmented by diverse chemical exposures.

<p>Treatment of HBEC-6KT human airway epithelial cells with ferric ammonium sulfate (50 μM), cycloheximide (0.01 μg/ml), H₂O₂ (100 μM), and dexamethasone (10 μg/ml) for 24h did not induce elevations in extracellular uric acid levels in contrast to the positive control of HDM (50 μg/ml). Data represent mean +/- SD, n = 3. Significance is represented by * = p<0.05 relative to control.</p

TNF-α and IFN-γ elevate extracellular uric acid levels and XDH gene expression in human airway epithelial cells.

<p><b>(A)</b> HBEC-6KT human airway epithelial cells were treated with TNF-α (20ng/ml) and IFN-γ (1000U/ml) for 24h followed by analysis of cell culture supernatant for uric acid levels in the presence or absence of allopurinol (500 μM) <b>(B)</b> <i>XDH</i> gene expression following TNF-α (20ng/ml) and IFN-γ (1000U/ml) treatment for 24h. Data represent mean +/- SD, n = 3. Significance is represented by * = p<0.05 relative to DMSO/control, % = p<0.05 relative to DMSO/ TNF-α+IFN-γ</p

Exposure to HDM but not cigarette smoke induces uric acid production <i>in vivo</i> in mouse lungs and <i>in vitro</i> in human airway epithelial cells.

<p>(<b>A</b>) BAL analysis of uric acid levels in mice 24h following exposure to air or cigarette smoke (n = 10). (<b>B</b>) BAL analysis of uric acid levels in mice 24h following exposure to PBS or HDM (n = 10). (<b>C</b>) HBEC-6KT human airway epithelial cell culture supernatant analysis of uric acid levels 24h following exposure to control (media alone) or cigarette smoke (4% cigarette smoke extract conditioned media) (n = 6). (<b>D</b>) HBEC-6KT human airway epithelial cell culture supernatant analysis of uric acid levels 24h following exposure to control (PBS) or HDM (50 μg/ml) (n = 6). Data represent mean +/- SD. Significance is represented by * = p<0.05 relative to control.</p