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DIESEL EXHAUST ENHANCES TOLL-LIKE RECEPTOR 3 EXPRESSION AND SIGNALING IN RESPIRATORY EPITHELIAL CELLS
Citation:
CIENCEWICKI, J., L. BRIGHTON, W. WU, M. C. MADDEN, AND I. JASPERS. DIESEL EXHAUST ENHANCES TOLL-LIKE RECEPTOR 3 EXPRESSION AND SIGNALING IN RESPIRATORY EPITHELIAL CELLS. American Journal of Physiology - Lung Cellular and Molecular Physiology. American Physiological Society, Bethesda, MD, 290(6):L1154-63, (2006).
Impact/Purpose:
To examine the effect of DEas on the toll-like receptor 3 (TLR3) pathway, which is responsible for the recognition of and response to viruses and double stranded RNA
Description:
Our previous studies have shown that prior exposure of respiratory epithelial cells to an aqueous-trapped solution of DE (DEas) enhances the susceptibility to Influenza infections. Here we examined the effect of DEas on the toll-like receptor 3 (TLR3) pathway, which is responsible for the recognition of and response to viruses and double stranded RNA. Flow cytometric and confocal microscopy analysis showed that TLR3 is predominantly expressed in the cytoplasm of respiratory epithelial cells. To examine the effect of DE on TLR3 expression and function, differentiated human bronchial or nasal epithelial cells as well as A549 cells were exposed to DEas and then infected with Influenza A or treated with polyriboinosinic acid:polyribocytidylic acid (poly(I:C)), a synthetic form of dsRNA. TLR3 mRNA levels were significantly up-regulated only in cells that were exposed to DEas prior to infection with Influenza or stimulation with poly(I:C). Additionally, pre-exposure to DEas significantly increased the expression of IL-6 in response to poly(I:C). Overexpression of a dominant negative mutant of TRAF6 (dnTRAF6) reversed the effects of DEas on poly(I:C)-induced IL-6 expression, suggesting that the response was TLR3-dependent. Similarly, pre-exposure to DEas