Regulation of Chemokine Expression by Lipopolysaccharide In Vitro and In Vivo
Abstract
The host response to Gram negative LPS is characterized by an influx of inflammatory cells into host tissues which is mediated predominantly by the localized production of chemokines. The influx and activation of inflammatory leukocytes, in combination with their overproduction of proinflammatory mediators, are believed to result in the tissue damage that precedes the multiple organ failure and death associated with sepsis. The overall goal of this work was to identify cellular and molecular mechanisms that contribute to the differential regulation of chemokine expression in response to LPS, in an effort to enhance our understanding of the unique roles of individual chemokines in a disease process as complex as sepsis. Our in vitro examination of LPS-inducible chemokine genes revealed variability in the magnitude and kinetics of expression in response to LPS, as well as differential patterns of expression in response to various modulators of inflammation, endotoxin tolerance, and mediators of transcriptional regulation. When similarities in regulation were observed, the chemokine genes involved were not restricted to genes of like biological function or classification within a specific chemokine subfamily. These findings provide insight into the complexity of the regulatory mechanisms that may account for their selective expression and function in vivo. Next, we observed a profound and rapid induction of chemokines that were temporally and spatially regulated following LPS exposure in vivo. Not only do these findings underscore the contribution of chemokines to the inflammatory process that precedes the pathophysiology of sepsis, but also indicate unique functions in the regulation and progression of the inflammatory response during sepsis. Finally, our evaluation of mice with a targeted disruption in the gene encoding the neutrophil chemoattractant, KC, r
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 10, 2002
- Accession Number
- ADA421412
Entities
People
- Karen M. Kopydlowski
Organizations
- Uniformed Services University of the Health Sciences