Prostaglandin E2 in NSAID-exacerbated respiratory disease: protection against cysteinyl leukotrienes and group 2 innate lymphoid cells.

Abstract

The purpose of this review is to describe the recent advances that have been made in understanding the protective role of prostaglandin E2 (PGE2) in aspirin-exacerbated respiratory disease (AERD), known in Europe as NSAID-exacerbated respiratory disease (N-ERD). Decreased PGE2 signaling through the EP2 receptor in patients with AERD leads to an increase in leukotriene synthesis and signaling. Leukotriene signaling not only directly activates group 2 innate lymphoid cells and mast cells, but it also increases production of IL-33 and thymic stromal lymphopoietin. These cytokines drive Th2 inflammation in a suspected feed-forward mechanism in patients with AERD. Recent discoveries concerning the role of PGE2 in leukotriene synthesis and signaling in AERD, as well as downstream effects on group 2 innate lymphoid cells and mast cells, allow for a more comprehensive understanding of the pathogenesis of this disease. These discoveries also identify new paths of potential investigation and possible therapeutic targets for AERD.