EP2 inhibition restores myeloid metabolism and reverses cognitive decline

Ryan Lushington; Samuel Camilli; Francisco Pascual; Richard F Lockey; Narasaiah Kolliputi

doi:10.1016/j.jacig.2023.100082

EP2 inhibition restores myeloid metabolism and reverses cognitive decline

J Allergy Clin Immunol Glob. 2023 Feb 8;2(2):100082. doi: 10.1016/j.jacig.2023.100082. eCollection 2023 May.

Authors

Ryan Lushington¹, Samuel Camilli¹, Francisco Pascual¹, Richard F Lockey¹, Narasaiah Kolliputi¹

Affiliation

¹ Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa.

Abstract

Nonsteroidal anti-inflammatory drugs alleviate pain and inflammation by inhibiting the cyclooxygenase pathway. This pathway has various downstream effects, some of which are beneficial. Prostaglandin E₂ is a key downstream product in the cyclooxygenase pathway that modulates inflammation. A correlation between aging and increased expression of the prostaglandin E₂ receptor, EP2, has been associated with inflammatory processes, cognitive aging, angiogenesis, and tumorigenesis. Therefore, inhibition of EP2 could lead to therapeutic effects and be more selective than inhibiting cyclooxygenase-2. Studies suggest that inhibition of EP2 restores age-associated spatial memory deficits and synaptic proteins and impairs tumorigenesis. The data indicate that EP2 signaling is important in myeloid cell metabolism and support its candidacy as a therapeutic target.

Keywords: COX; EP2; PGE2 signaling; cognition; cognitive decline; inflammation; myeloid metabolism; prostaglandin E2; tumorigenesis.