You are here:
GENE PROFILING AND THE ROLE OF COAGULATION FACTORS IN INFLAMMATION SIGNALING IN HUMAN PULMONARY ARTERY ENDOTHELIAL CELLS FOLLOWING ULTRAFINE PARTICLES EXPOUSRE
Citation:
KAROLY, E. D., L. A. DAILEY, T. T. HUANG, AND Z. LI. GENE PROFILING AND THE ROLE OF COAGULATION FACTORS IN INFLAMMATION SIGNALING IN HUMAN PULMONARY ARTERY ENDOTHELIAL CELLS FOLLOWING ULTRAFINE PARTICLES EXPOUSRE. Presented at American Thoracic Society International Congress, San Diego, CA, May 19 - 24, 2006.
Description:
Epidemiologic studies have linked exposures to particulate air pollution and increased cardiovascular mortality and morbidity, however, the mechanisms are not clear. Ultrafine particles within air pollution represent a particular area of concern because the small size fraction of particles (< 100 nm) can be breathed most deeply into the lungs and may translocate into the circulation. In this study, we profiled gene expression pattern in human pulmonary artery endothelial cells (HPAEC) exposed to the ultrafine fraction of Chapel Hill particles (UTF). We focused on the relationship between coagulation and inflammation signaling. RNA from cultured HPAEC treated with UTF (100¿g/ml) or vehicle for 4h were hybridized to Affymetrix HG U133 Plus 2.0 chips. Differentially expressed genes were identified by the unpaired t-test (p <0.01), 5% false discovery rate) and a treatment/control ratio cutoff of > 1.5 or < 0.5. We found 99 genes to be differentially expressed. Several upregulated genes were related to coagulation and inflammation including tissue factor (F3), thrombin receptor-like 2 (F2RL2), interleukin 6 (IL6) and interleukin 8 (IL8). These results were confirmed independently by RT-PCR. Treatment of HPAEC with UTF for 16 hours increased the release of IL6 and IL8 by 1.9-fold and 1.8-fold respectively. Pretreatment of HPAEC with a blocking antibody against F3 attenuated IL6 and IL8 release by 30% and 70% respectively. Pretreatment with a thrombin inhibitor (Bivalirudin) also attenuated the UTF-stimulated release of IL6 and IL8 by 31% and 39% respectively. Thus using gene profiling, we uncovered that UTF may stimulate vascular inflammation via activation of the extrinsic coagulation pathway. These results provide a mechanistic link between UTF exposure and cardiovascular adverse health effects. (Abstract does not reflect USEPA policy).