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microRNA Regulation of DEP-induced Inflammation in Airway Epithelial Cells
Citation:
JARDIM, M. J., L. A. DAILEY, AND D. DIAZ SANCHEZ. microRNA Regulation of DEP-induced Inflammation in Airway Epithelial Cells. Presented at Society of Toxicology Annual Meeting, Washington, DC, March 06 - 10, 2011.
Impact/Purpose:
author invited to present
Description:
Morbidity and mortality attributable to air pollution continues to be a growing problem worldwide. Despite several studies on the health effects of ambient air pollution, underlying molecular mechanisms of susceptibility and disease remain elusive. The epigenome controls gene expression without affecting the DNA sequence itself and it can be inherited from generation to generation. It is not currently understood how exposure to air pollutants can modify underlying epigenetic mechanisms to elicit cellular responses such as inflammation. MicroRNAs are small noncoding RNAs that have been quickly established as key regulators of gene expression. As such, miRNAs have been found to control several cellular processes including apoptosis, proliferation and differentiation. We have previously shown that exposure to diesel exhaust particles (DEP) induces a rapid change in the expression of several microRNAs in human bronchial epithelial cells (BECs). Molecular network analysis of hsa-miR-513 suggested that the putative targets ofthis miRNA were enriched for regulators of the inflammatory response, including IL8 and COX2. We hypothesized that this miRNA plays an important role in attenuating the inflammatory response after exposure to DEP by regulating IL8 and COX2 mRNA levels. Indeed, over-expression of miR-513a leads to an attenuation of DEP induced IL8 and COX2. Alternatively, induced knockdown of this microRNA resulted in heightened levels of IL8 and COX2 mRNA in the presence of DEP, suggesting that miR-513a may be acting as a negative regulator of the inflammatory response. Furthermore, induction of miR-513a upon stimulation with DEP implies that it may playa role in a negative feedback loop which serves to attenuate the inflammatory response once critical levels of inflammatory mediators have been achieved. THIS ABSTRACT OF A PROPOSED PRESENTATION DOES NOT NECESSARILY REFLECT EPA POLICY.