%0 Journal Article %A Toshihisa Inada %A Keita Arai %A Michiko Kawamura %A Ko Hatanaka %A Yuichi Sato %A Makoto Noshiro %A Yoshiteru Harada %T Contribution of the Prostaglandin E2/E-Prostanoid 2 Receptor Signaling Pathway in Abscess Formation in Rat Zymosan-Induced Pleurisy %D 2009 %R 10.1124/jpet.109.155358 %J Journal of Pharmacology and Experimental Therapeutics %P 860-870 %V 331 %N 3 %X Abscess formation is a classic host response to infection by many pathogenic microorganisms. Here, we studied the role of prostaglandins (PGs) and their signal transduction in abscess formation. Zymosan was injected into the pleural cavity of rats. Expression of enzymes involved in PG synthesis, their receptors, and cytokines in exudate leukocytes and abscesses were analyzed by polymerase chain reaction, Western blotting, and immunohistochemistry. Treatment with ketorolac, a cyclooxygenase (COX)-1 inhibitor, or N-[2-cyclohexyloxy-4-nitrophenyl] methanesulfonamide (NS-398), a COX-2 inhibitor, reduced the size of abscesses and the number of cells recovered from the abscess. COX-2 was detected in leukocytes of the exudate and a marginal area of abscesses. Among detected terminal PG synthases, the major one was cytosolic PGE synthase. Membrane-bound PGE synthase (mPGES)-1 was detected in cells that were similar to the COX-2-expressing cells in morphology and localization. A high level of the E-prostanoid (EP)2 receptor and a low level of the EP4 receptor were detected. The expression pattern of the EP2 receptor paralleled that of COX-2 and mPGES-1. 11,15-O-Dimethyl PGE2 (ONO-AE1-259), an EP2 receptor agonist, and rolipram, a phosphodiesterase type-4 inhibitor, reversed the effects of COX inhibitors on abscess formation. In contrast, 16-(3-methoxymethyl) phenyl-ω-tetranor-3,7-dithia PGE1 (ONO-AE1-329), an EP4 receptor agonist, did not reverse the effects of NS-398. Moreover, NS-398 reduced the mRNA levels in exudate leukocytes of some proinflammatory and fibrogenic cytokines, which was reversed by ONO-AE1-259. These results suggest that PGE2 generated via COX-1 and COX-2 may interact with the EP2 receptor and may up-regulate in cAMP-dependent fashion the production of cytokines that promote abscess formation.© 2009 by The American Society for Pharmacology and Experimental Therapeutics %U https://jpet.aspetjournals.org/content/jpet/331/3/860.full.pdf