Regulation of Immune Responses by Prostaglandin E2

Abstract

Prostaglandin E2 (PGE2), an essential homeostatic factor, is also a key mediator of immunopathology in chronic infections and cancer. The impact of PGE2 reflects the balance between its COX2-regulated synthesis and 15-PGDH-driven degradation, and the pattern of expression of PGE2 receptors. PGE2 enhances its own production, but suppresses acute-inflammatory mediators, resulting in its predominance at late/chronic stages of immunity. PGE2 supports activation of dendritic cells, but suppresses their ability to attract naïve, memory- and effector T cells. PGE2 selectively suppresses effector functions of macrophages and neutrophils and the Th1-, CTL- and NK cell-mediated type-1 immunity, but promotes Th2, Th17, and Treg responses. PGE2 modulates chemokine production, inhibiting the attraction of pro-inflammatory cells, while enhancing local accumulation of Treg cells and myeloid-derived suppressor cells. Targeting the production, degradation and responsiveness to PGE2, provides tools to modulate the patterns of immunity in a wide range of diseases, from autoimmunity to cancer.

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“…Prostaglandins (PGs) are small-molecular derivatives of arachidonic acid, produced by cyclooxygenases (COXs; constitutively active cyclooxygenase COX-1 and inducible COX-2) and PG synthases [93]. COX-2 expression is induced by cytokines and growth factors at sites of inflammation and is usually not detected in normal tissues [94].…”

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