MOLECULAR MECHANISMS OF MACROPHAGE ACTIVATION BY LPS

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We have been interested in the mechanisms of host defense against neoplastic cells. When macrophages are stimulated with bacterial lipopolysaccharide (LPS), they become highly cytotoxic to a variety of neoplastic cells. In order to understand the molecular mechanisms involved in this process, we plan to (l) characterize the LPS-responsive elements (LRE) in promoter regions of the immediate early genes transcriptionally activated by LPS, (2) characterize and isolate transcription factor(s) that become associated with LRE and (3) isolate the gene called lps that controls the responsiveness of mouse and murine macrophages to LPS. The responses of macrophages to LPS stimulation can occur without the participation of T or B lymphocytes, and may very well represent a primitive defense reaction against potential pathogens. Elucidation of molecular mechanisms involved in this process will advance our understanding of septic shock caused by LPS, action of anticancer drug Taxol, as well as natural immunity against a variety of potentially harmful agents including virus and neoplastic cells.