PGE2 suppression of innate immunity during mucosal bacterial infection

Abstract

Prostaglandin E2 (PGE2) is an important lipid mediator in inflammatory and immune responses during acute and chronic infections. Upon stimulation by various proinflammatory stimuli such as lipopolysaccharide (LPS), interleukin (IL)-1β, and tumor necrosis factor (TNF)-α, PGE2 synthesis is upregulated by the expression of cyclooxygenases. Biologically active PGE2 is then able to signal through four primary receptors to elicit a response. PGE2 is a critical molecule that regulates the activation, maturation, migration, and cytokine secretion of several immune cells, particularly those involved in innate immunity such as macrophages, neutrophils, natural killer cells, and dendritic cells. Both Gram-negative and Gram-positive bacteria can induce PGE2 synthesis to regulate immune responses during bacterial pathogenesis. This review will focus on PGE2 in innate immunity and how bacterial pathogens influence PGE2 production during enteric and pulmonary infections. The conserved ability of many bacterial pathogens to promote PGE2 responses during infection suggests a common signaling mechanism to deter protective pro-inflammatory immune responses. Inhibition of PGE2 production and signaling during infection may represent a therapeutic alternative to treat bacterial infections. Further study of the immunosuppressive effects of PGE2 on innate immunity will lead to a better understanding of potential therapeutic targets within the PGE2 pathway.

Leishmania donovani-Induced Prostaglandin E2 Generation Is Critically Dependent on Host Toll-Like Receptor 2–Cytosolic Phospholipase A2 Signaling

“…A growing body of evidence highlights the importance of this lipid mediator in the immunopathology of cancer (5-7) and infectious diseases caused by protozoa, viruses, and bacteria (4,(32)(33)(34)(35). Several species of Leishmania are reported to upregulate macrophage PGE2 production and to exploit the immunosuppressive properties of PGE2 to survive within the hostile intramacrophagic environment (13,36,37).…”

E-Prostanoid 2 Receptor Overexpression Promotes Mesenchymal Stem Cell Attenuated Lung Injury

“…10,11 Nonsteroidal antiinflammatory drugs inhibit PGE 2 synthesis, and it is thus designated as a potent proinflammatory modulatory molecule. 12 Emerging evidence now suggests that PGE 2 has antiinflammatory properties.…”

Colonic Saturated Fatty Acid Concentrations and Expression of COX-1, but not Diet, Predict Prostaglandin E2in Normal Human Colon Tissue

“…In normal tissues, however, this is not entirely clear. In the immune cells, for example, PGE 2 has a role in dampening and resolving inflammatory responses to infection (40). …”