Accession Number : AD1011440


Title :   Regulation of Intracellular Signaling Leading to Gene Expression in Lipopolysaccharide Stimulated Murine Macrophages


Descriptive Note : Technical Report


Corporate Author : Uniformed Services University Of The Health Sciences Bethesda United States


Personal Author(s) : Barber,Sheila


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/1011440.pdf


Report Date : 20 Sep 1995


Pagination or Media Count : 248


Abstract : Due to the ubiquitous nature of LPS and its causative relationship to Gram negative sepsis, the study of LPS-induced cellular responses has been an area of active research for well over a decade. Earlier studies revealed that LPS stimulation results in the production of a cascade of proinflammatory mediators, such as cytokines. Recent studies have attempted to unravel the intricacies of the LPS signaling pathways that lead to cytokine production, in the hope of uncovering potentially vulnerable targets for pharmacologic intervention in septic shock. The studies presented herein were designed with such a purpose in mind. At the cellular level, manipulation of the LPS response in macrophages may occur at the plasma membrane, in the cytoplasm, or in the nucleus, and thus, we examined the regulation of LPS-induced gene expression at each of these levels. The studies of nuclear regulation focused on an evaluation of the role of Interferon Regulatory Factors (IRFs) in LPS-induced gene expression. The results suggest that while IRFs contribute to the regulation of LPS-inducible genes, the development of agents that may inhibit the function of these proteins may be of little use in combating sepsis, as LPS-induced immediate-early cytokine gene expression is essentially unaffected in macrophages derived from IRF knock-out mice.


Descriptors :   Gene Expression , Lipopolysaccharides , Macrophages , cell physiological processes , response (biology) , Interferon , Sepsis , Endotoxins , cytokines , metabolism , phosphorylation , phosphorous transferases , nucleotides , cells (biology) , proteins , ribonucleic acids , PHOSPHATASES


Distribution Statement : APPROVED FOR PUBLIC RELEASE