Prostaglandin E_𝟐 and the Suppression of Phagocyte Innate Immune Responses in Different Organs

Figure 2

PGE₂ receptors and their actions in macrophages. PGE₂ produced during inflammatory conditions binds to EP₂, EP₄, EP₃, or EP₁. EP₂ and EP₄ are coupled to G𝛼_𝑠, and the binding of PGE₂ to these G protein-coupled receptors (GPCRs) induces a conformational change that results in the liberation of the G𝛼_𝑠 subunit from the Gβ γ subunit complex. The binding of the Gα subunit to adenylyl cyclase (AC) either stimulates (G𝛼_s) or inhibits (G𝛼_i, via EP₃ signaling) the enzyme’s generation of cAMP. The production of cAMP is also regulated by microbial pathogens. Downstream cAMP signaling is mediated by its interactions with effector molecules, such as protein kinase A (PKA), or exchange proteins that are directly activated by cAMP (Epac), which have been shown to modulate phagocyte functions. Depicted here is a pattern for alveolar macrophages in which specific antimicrobial functions are differentially regulated by specific cAMP effectors.