INTERLEUKIN 1 SYNTHESIS AND SECRETION

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The results from numerous studies indicate that interleukin 1 (IL 1), a low molecular weight protein produced by stimulated macrophages and perhaps several other cell types, can markedly affect the maturation, functional activation, and proliferation of a broad range of cell types that share a common involvement in immune or inflammatory responses. In view of the proposed role of IL 1 in immunity and inflammation, it is important to understand the pathway(s) and regulation of IL 1 synthesis, release, and extracellular processing, as well as its mechanism of action at the molecular level. Thus the major goals of this proposal are: To elucidate the sequence of events that occur between the synthesis of the 33,000 molecular weight (m.w.) IL 1 precursor in stimulated human and murine monocytes/macrophages and the appearance of low m.w. IL 1 (17-19,000) in the extracellular environment; to define the amino acid sequence(s) in the IL 1 precursor that serves to target this protein for secretion; to determine the amino acid sequences in the IL 1 precursor that serve as primary sites for extracellular processing; and to elucidate the mechanism by which calcium enhances the secretion of IL 1 as well as its extracellular processing. In the work outlined in this proposal, we will depend on the use of recombinant forms of precursor and low molecular weight human and murine IL 1, highly specific anti-IL 1 antibodies, and IL 1 cDNA probes.