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COMPARISON OF PM-INDUCED GENE EXPRESSION PROFILES BETWEEN BRONCHIAL EPITHELIAL CELLS AND NASAL EPITHELIAL CELLS IN HUMAN
KAROLY, E., L. BRIGHTON, I. JASPERS, J. CARSON, AND Y. T. HUANG. COMPARISON OF PM-INDUCED GENE EXPRESSION PROFILES BETWEEN BRONCHIAL EPITHELIAL CELLS AND NASAL EPITHELIAL CELLS IN HUMAN. Presented at American Thoracic Society Annual Meeting, San Francisco, CA, May 18 - 23, 2007.
Epidemiologic studies have linked exposures to particulate matter (PM) and increased pulmonary mortality and morbidity. Bronchial epithelial cells (BEC) are the primary target of PM. PM exposure induces a wide array of biological responses in BEC. Primary human BEC, however, need to be obtained by bronchoscopy. Since nasal epithelial cells (NEC) have similar cellular morphology and can be obtained by nasal biopsy, a less invasive procedure than bronchoscopy, we hypothesized that NEC may be used as a surrogate cell type for BEC to assess PM lung toxicity. We obtained BEC and NEC by bronchoscopy and nasal biopsy respectively from 4 normal individuals and cultured them in air liquid interface for 6-8 weeks. We treated these cells with 100 µg/ml of fine fraction of Chapel Hill particles or vehicle for 4 hours. RNA was isolated and hybridized to Affymetrix HG U133 Plus 2.0 chips. 53.8% of the probes were concordantly altered in the same direction by PM in BEC and NEC. The Kendall's coefficient (ι) between BEC and NEC of mean PM/control ratio was 0.074 (P < 0.0001). Using a paired t-test (p <0.05), we identified 3,121 and 2,186 probes induced by PM in BEC and NEC respectively. Using a Venn diagram, we found 174 probes common to BEC and NEC, including upregulation of CYP1A1, CYP1B1, IL1A, IL1¿¿ IL1RN and PTGS2 (COX2). The hierarchical clustering analysis of these probes showed CYB1A1 and CYP1B1 genes were clustered with IL1¿ and PTGS2, IL1RN, and SERPINB2 respectively. Our results showed that gene expression patterns in BEC and NEC in response to PM exposure in vitro had significant similarity. NEC may be used as a surrogate cell type to assess acute pulmonary effects of PM in normal and susceptible population, such as asthma (Abstract does not reflect USEPA policy).
Record Details:Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
HUMAN STUDIES DIVISION
CLINICAL RESEARCH BRANCH