Interleukin-1 Mediated Effects of Ozone in the LungEPA Grant Number: GF9501896
Title: Interleukin-1 Mediated Effects of Ozone in the Lung
Investigators: Pearson, Alison
Institution: University of California - Irvine
EPA Project Officer: Michaud, Jayne
Project Period: September 1, 1995 through January 1, 2000
Project Amount: $37,350
RFA: STAR Graduate Fellowships (1995) Recipients Lists
Research Category: Fellowship - Health , Health Effects , Academic Fellowships
Exposure to ozone (03) is known to induce pulmonary inflammation, characterized by an influx of neutrophils (PMNs) into the trachea and bronchoalveolar space , and epithelial permeability changes indicated by an increase in serum proteins in lavage fluid. The acute inflammatory processes are mediated, primarily, by phagocytic cells such as macrophages and PMNs. An important chemical mediator which is released by these cell types and to which they respond is interleukin-1 (IL-1). Since exposure to O3 leads to inflammation in the lung and IL-1 is known to be involved in that process, it can be hypothesized that ozone exposure induces a measurable change in the release of IL-1 and surface expression of its receptor. The intent of this project is to test the above hypothesis and to correlate any such changes to markers of lung inflammation by accomplishing the six goals that follow. The six goals that have been set forth to test the hypothesis are: 1) to document the expression of cell-associated IL-1 by lavageable cells and lung tissues at discrete time points following in vivo exposure to O3.
IL-1 will be immunohistochemically localized using antibiotics conjugated to a fluorescent moiety. Fluorescence can then be induced and quantified on a per cell basis via laser cytometry. If this is found to be altered, then O3 affects the synthesis of the protein, the translation of pre-transcribed message, or it disrupts cellular mechanisms for protein release from cytoplasmic stores, 2) to measure the release of IL-1 by lung tissues and inflammatory cells into lavage fluid as a function of time and concentration of O3, 3) to examine correlations between changes in cell-associated IL-1 and its release and alterations in permeability, neutrophil influx, and the development of edema that result from O3 exposure via appropriate statistical analysis. This would isolate the chronological relationship between exposure, initiation of the cytokine cascade, and pathophysiological changes in the lung, 4) to document any changes in surface expression of the IL-1 receptor on lavageable cells and lung tissue as a function of time and concentration of O3, 5) construction of an accurate description of the time-dependent changes in IL-1 release and surface expression of the receptor as they relate to exposure and measures of permeability and edema, and 6) to explore the efficacy of antagonism of components of the IL-1 system on in vivo and in vitro responses to O3 to provide corroborative evidence that IL-1 and its receptor are involved in the response.