Effects of PM2.5 collected from Cache Valley Utah on genes associated with the inflammatory response in human lung cells.
In January 2004, the normally picturesque Cache Valley in northern Utah made national headlines with the highest PM2.5 levels in the nation. Epidemiological studies linked exposure to particulate air pollution in other locations with stroke and Alzheimer's disease and to early mortality from all causes, cancer, and cardiopulmonary diseases. To determine potential effects of these particles on human health, human bronchial epithelial cells (BEAS-2B) were cultured with PM2.5 collected from various locations in the Cache Valley. These particles were slightly cytotoxic, but more potent than NH4NO3, the major chemical component of Cache Valley PM2.5. Gene expression analysis of PM2.5-exposed cells was performed using microarray and quantitative reverse-transcription polymerase chain reaction (RT-PCR). Among other genes, PM2.5 exposure induced genes and proteins involved in the inflammatory response. Most notably, PM2.5-exposed cells showed significant gene level upregulation of activating receptors to interleukins 1 and 6 (IL-1R1 and IL-6R), as well as concomitant increases in protein. Increases in IL-1 receptor associated kinase-1 (IRAK) protein were observed. PM2.5 exposure resulted in release of IL-6, as well phosphorylated STAT3 protein, providing evidence that PM activates the IL-6/gp130/STAT3 signaling pathway in BEAS-2B cells. IL-20 and major histocompatibility complex peptide class-1 (MICA) were upregulated and cleavage of caspase-12 was detected. In total, our results indicate that Cache Valley PM2.5 produces the upregulation of important cytokine receptors and is able to activate both IL-1R- and IL-6R-mediated signaling pathways in human lung cells. These observations are generally consistent with the adverse effects associated with inhalation of fine particulate matter like PM2.5.
Watterson
Todd L
TL
Graduate Program in Toxicology, Department of Veterinary Sciences, Utah State University, Logan, Utah 84322-4620, USA.
Sorensen
Jared
J
Martin
Randy
R
Coulombe
Roger A
RA
D053148:Caspase 3 / Q000187:drug effects; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D007378:Interleukins / Q000235:genetics*; D008168:Lung / Q000187:drug effects*; D009566:Nitrates / Q000032:analysis / Q000633:toxicity; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D052638:Particulate Matter / Q000032:analysis / Q000633:toxicity*; D014589:Utah
D007378:Interleukins; D009566:Nitrates; D052638:Particulate Matter; D053148:Caspase 3; C006568:ammonium nitrate