The Immunobiology of Prostanoid Receptor Signaling in Connecting Innate and Adaptive Immunity

Hedi Harizi

doi:10.1155/2013/683405

Abstract

Prostanoids, including prostaglandins (PGs), thromboxanes (TXs), and prostacyclins, are synthesized from arachidonic acid (AA) by the action of Cyclooxygenase (COX) enzymes. They are bioactive inflammatory lipid mediators that play a key role in immunity and immunopathology. Prostanoids exert their effects on immune and inflammatory cells by binding to membrane receptors that are widely expressed throughout the immune system and act at multiple levels in innate and adaptive immunity. The immunoregulatory role of prostanoids results from their ability to regulate cell-cell interaction, antigen presentation, cytokine production, cytokine receptor expression, differentiation, survival, apoptosis, cell-surface molecule levels, and cell migration in both autocrine and paracrine manners. By acting on immune cells of both systems, prostanoids and their receptors have great impact on immune regulation and play a pivotal role in connecting innate and adaptive immunity. This paper focuses on the immunobiology of prostanoid receptor signaling because of their potential clinical relevance for various disorders including inflammation, autoimmunity, and tumorigenesis. We mainly discuss the effects of major COX metabolites, PGD2, PGE2, their signaling during dendritic cell (DC)-natural killer (NK) reciprocal crosstalk, DC-T cell interaction, and subsequent consequences on determining crucial aspects of innate and adaptive immunity in normal and pathological settings.

Highlights

Prostanoids are biologically active molecules that have various and potent effects on almost all cells and tissues in physiological and pathophysiological conditions [1]
Known as potent inflammatory lipid mediators, prostanoids may function in both the promotion and resolution of the inflammatory response [3]. Their biosynthesis is suppressed by nonsteroidal anti-inflammatory drugs (NSAIDs) that are clinically relevant molecules widely consumed as analgesics or antipyretics drugs
Epidemiological studies have provided evidence that NSAIDs that inhibit PG synthesis by acting on COX enzymes can significantly reduce the risk of cancer development [5], suggesting that prostanoids may play a key role in tumorigenesis

Summary

Introduction

Prostanoids are biologically active molecules that have various and potent effects on almost all cells and tissues in physiological and pathophysiological conditions [1]. Given the potent immunomodulatory effects of PGD2 and PGE2 [25,26,27], it is not surprising that cells that produced large amounts of these lipid mediators are considered to be the most powerful modulators of inflammatory processes and immune function. For these reasons, understanding how prostanoid receptor signaling affect immune cell crosstalk and functions may be exploited for rational development of immunotherapeutic strategies in various diseases ranging from inflammation and allergic diseases to cancer. Epigenetic modifications in prostanoid genes represent additional levels of complexity for understanding immunological processes involved in normal and pathological settings

Differential Profile of Prostanoid Biosynthesis in Immune Cells

Prostanoid Receptor

Epigenetic Modifications of Prostanoids

Concluding Remarks