Effects of PM_2.5 Collected from Cache Valley Utah on Genes Associated with the Inflammatory Response in Human Lung Cells

Abstract

In January 2004, the normally picturesque Cache Valley in northern Utah made national headlines with the highest PM_2.5 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 PM_2.5 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 PM_2.5. Gene expression analysis of PM_2.5-exposed cells was performed using microarray and quantitative reverse-transcription polymerase chain reaction (RT-PCR.) Among other genes, PM_2.5 exposure induced genes and proteins involved in the inflammatory response. Most notably, PM_2.5-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. PM_2.5 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 PM_2.5 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 PM_2.5.

The authors thank Lorinda Anderson and Dr. John Veranth of the University of Utah for performing the IL-6 ELISA and Dr. Jeffrey Hall and John Guarisco for their critical reviews of the article. This work was supported in part by grants from the Marriner S. Eccles Foundation, the Utah Water Research laboratory, the Center for Integrated Biosystems at Utah State University, and by the Utah Agricultural Experiment Station, where it is paper number 7830.

Portions of this report were presented at the 45th annual meeting of the Society of Toxicology, San Diego, CA, March 2006 (Abstract 237).