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Regulation of cAMP in Macrophages

The production of cAMP in macrophages can markedly alter the spectrum of cytokines secreted in response to activators of the cells and, in general, is thought to provide an anti-inflammatory response. The dual ligand screen in RAW cells, conducted by the AfCS during the initial 5 year funding period, elucidated several synergistic interactions for the production of this second messenger. Stimulation of cAMP by two Gs coupled receptors (α2-adrenergic and prostaglandin E2) gave less than additive responses when combined. However, five ligands (UDP, PAF, LPA, C5a and S1P), which did not stimulate cAMP by themselves, caused synergistic increases in cAMP production that was simultaneously stimulated by the Gs pathways. Current studies are focused on determining the mechanisms of these interactions, elucidating novel pathways and initiating molecular modeling of this signaling module.

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