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Cytokine release

Modulation of Cytokine Secretion by Macrophages

A major initiative of the AfCS was "to provide an experimental assessment of functional interactions between stimuli in one cell type" as assessed through the measured responses of multiple outputs. A major downstream output was the measurement and analysis of 18 secreted cytokines (G-CSF, GM-CSF, IFN-γ, IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-10,IL-12(p40), IL-12(p70), IL-17, KC, MIP-1α, Rantes, and TNF-α). This screen identified multiple pathways that modulate the release of cytokines stimulated by Toll-like receptor ligands. The Cytokine project is currently subdivided into two projects: 1) The first project employshigher-order ligand screens to identify putative interactions and synergies between ligand/receptor signaling pathways that influence secreted cytokine profiles. 2) The second project capitalizes on the observation from the paired ligand screen that cAMP inducing ligands, Prostaglandin E2 and Isoproterenol, and cAMP itself differentially regulate the secretion of the LPS-dependent cytokines, G-CSF, IL-6, IL-10, TNF-α, and MIP1-α, in these cells. The goal is to determine the mechanisms by which this regulation through cAMP is achieved.

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