Control of Cytokine Gene Expression in Macrophages: Role of Second Messenger Pathways
Annual rept. no. 1, Nov 88-Oct 89
STRITCH SCHOOL OF MEDICINE MAYWOOD IL DEPT OF ANATOMY
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The overall objective of this project is to enhance our understanding of the intracellular second messenger pathways involved in the regulation of the expression of soluble cellular mediator cytokine genes in macrophages by bacterial lipopolysaccharide LPS and interluekin-2 IL-2. One aim of this study is to directly examine the mechanisms of action of LPS and IL-2 on the expression of two potent immunomodulatory and cytotoxic cytokines interleukin-1 IL-1 alpha and beta and tumor necrosis factor alpha TNFalpha. During Year 1, an analysis of the second messenger pathways involved in the expression of IL-1beta mRNA has been initiated. These studies involved a comparison of protein kinase C and calmodulin kinase involved in the transduction of signals initiated by IL-2 and LPS which lead to the expression of IL-1beta mRNA in human monocytes. Another aim of the project involves an examination of the expression of fibrogenic cytokines, including transforming growth factor-beta TGFbeta, platelet-derived growth factor PDGF and fibroblast growth factor FGF, which have been implicated in models of wound healing and fibrosis. Studies initiated in the past several months have examined the kinetics of expression of TGFbeta, PDGF A chain and PDGF B chain mRNAs in monocypes.
- Genetic Engineering and Molecular Biology