Prostaglandin E2 Receptors of Monocytes/Macrophages: Regulation by Insulin and Interleukin-1α

The regulation of receptors for prostaglandin E₂ (PGE₂) in monocyte/macrophage-like cells, P388D₁, by interleukin-1α (IL-1α) and insulin has been investigated. Many of the effects of IL-1, such as fever and other inflammatory activities, are linked to the stimulation of PGE₂ synthesis. On the other hand, PGE₂ exhibits suppressive effects on many steps in the immune response, including IL-1 production. The binding of PGE₂ to monocytes is reported to be essential for the inhibition of IL-1 production and activity. This inhibition occurs through the stimulation of cyclic AMP synthesis by the activation of PGE₂ receptor-linked adenylate cyclase. Although IL-1α stimulates PGE₂ synthesis in monocytes/macrophages during immunoactivation, it inhibits the binding of PGE₂ to these cells and may thereby exert a countervailing effect on the immunosuppressive action of this prostanoid. By contrast, insulin at physiological concentrations enhances the PGE₂ binding to these cells. This suggests that insulin at physiological concentrations may enhance the immunosuppressive action of PGE₂. Since the stimulation of cAMP synthesis in cells is regulated by PGE₂ binding, it is possible that these hormonal factors may control the immune response by modulating the PGE₂ receptor activity of monocytes/macrophages. This article focuses on the interactions of insulin and IL-1 with PGE₂ receptors of monocytes/macrophages.