Prostaglandin E 2 as a Regulator of Immunity to Pathogens

Abstract

The body is exposed to foreign pathogens every day, but remarkably, most pathogens are effectively cleared by the innate immune system without the need to invoke the adaptive immune response. Key cellular components of the innate immune system include macrophages and neutrophils and the recruitment and function of these cells are tightly regulated by chemokines and cytokines in the tissue space. Innate immune responses are also known to regulate development of adaptive immune responses often via the secretion of various cytokines. In addition to these protein regulators, numerous lipid mediators can also influence innate and adaptive immune functions. In this review, we cover one particular lipid regulator, prostaglandin E (PGE) and describe its synthesis and signaling and what is known about the ability of this lipid to regulate immunity and host defense against viral, fungal and bacterial pathogens.

Upregulation of PD-L1 Expression by Prostaglandin E2 and the Enhancement of IFN-γ by Anti-PD-L1 Antibody Combined With a COX-2 Inhibitor in Mycoplasma bovis Infection

“…However, further studies focusing on TLR4 and M. bovis must be needed to elucidate the relationship between M. bovis infection and PGE 2 . PGE 2 suppresses Th1 immune responses, limiting the functions of natural killer (NK) cells, CD4 T cells, and cytotoxic T cells via specific EP2 and EP4 receptors (14). After binding EP2 or EP4, PGE 2 induces the expression of anti-inflammatory and immunosuppressive genes by activating the cyclic AMP (cAMP)/protein kinase A/cAMP response element binding protein pathway (14).…”

“…Prostaglandin E 2 (PGE 2 ) is one of the lipid mediators that are derived from arachidonic acid synthesized by cyclooxygenase isoenzymes (COX-1 and COX-2) (12,13). It is known that PGE 2 promotes the immune dysfunction associated with several tumors and chronic inflammation (14,15). Interestingly, recent reports on cancer have shown a relationship between PGE 2 and the PD-1/PD-L1 pathway (16,17).…”

Decidual stromal cell‐derived PGE2 regulates macrophage responses to microbial threat

“…Prostaglandins (PGs) are ubiquitous lipid mediators derived from cyclooxygenase (COX)-dependent metabolism of arachidonic acid, an omega-6 polyunsaturated fatty acid found in cell membrane phospholipids 20 . PGs are involved in many aspects of parturition, including maternal immune tolerance to the fetus 21–24 and labor 25–28 .…”

“…[16][17][18][19] Prostaglandins (PGs) are ubiquitous lipid mediators derived from cyclooxygenase (COX)-dependent metabolism of arachidonic acid, an omega-6 polyunsaturated fatty acid found in cell membrane phospholipids. 20 PGs are involved in many aspects of parturition, including maternal immune tolerance to the fetus [21][22][23][24] and labor. [25][26][27][28] One particular PG, PGE 2 , has potent immunomodulatory actions on both innate and adaptive immunity 20,[29][30][31][32][33] and has been implicated as a decidual stromal cell-derived paracrine mediator of lymphocyte and natural killer cell function.…”

“…20 PGs are involved in many aspects of parturition, including maternal immune tolerance to the fetus [21][22][23][24] and labor. [25][26][27][28] One particular PG, PGE 2 , has potent immunomodulatory actions on both innate and adaptive immunity 20,[29][30][31][32][33] and has been implicated as a decidual stromal cell-derived paracrine mediator of lymphocyte and natural killer cell function. [22][23][24] The extent to which PGE 2 or other PGs explain paracrine immunoregulation between decidual stromal cells and macrophages is not well defined.…”