Development of a flow-cytometry-based method to measure the expression of cell surface molecules on endothelial cells is proposed for screening for novel regulators of inflammation. Many anti-inflammatory drugs, including corticosteroids, cyclooxygenase inhibitors and lipoxygenase inhibitors, inhibit the cytokine-dependent expression of certain endothelial cell surface molecules in culture. Our preliminary studies indicate that drugs can be distinguished based on their selective effects on particular cell surface molecules and/or under particular activation conditions. A robust assay system that can rapidly measure these effects under conditions that are more relevant to complex disease processes may be a useful tool for the rapid identification and characterization of novel anti-inflammatory drug compounds. The development of a multi-parameter flow cytometry method that allows the simultaneous measurement of multiple cell surface molecules in such a system may provide an innovative strategy for identifying and characterizing novel regulators of inflammation from synthetic or natural product libraries.
Commercial application: identifying anti-inflammatory drug compounds for pharmaceutical drug discovery.
Berg, E L; Kunkel, E J; Hytopoulos, E (2005) Biological complexity and drug discovery: a practical systems biology approach. Syst Biol (Stevenage) 152:201-6 |
Plavec, Ivan; Sirenko, Oksana; Privat, Sylvie et al. (2004) Method for analyzing signaling networks in complex cellular systems. Proc Natl Acad Sci U S A 101:1223-8 |
Kunkel, Eric J; Dea, Marlene; Ebens, Allen et al. (2004) An integrative biology approach for analysis of drug action in models of human vascular inflammation. FASEB J 18:1279-81 |
Kunkel, Eric J; Plavec, Ivan; Nguyen, Dat et al. (2004) Rapid structure-activity and selectivity analysis of kinase inhibitors by BioMAP analysis in complex human primary cell-based models. Assay Drug Dev Technol 2:431-41 |