| Title | Contribution of the prostaglandin E2/EP2 receptor-signaling pathway in abscess formation in rat zymosan-induced pleurisy. | | Author(s) | Inada T, Arai K, Kawamura M, Hatanaka K, Sato Y, Noshiro M, Harada Y | | Institution | Kitasato University. | | Source | J Pharmacol Exp Ther 2009 Sep 2. | | Abstract | 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 NS-398, a COX-2 inhibitor, reduced size of abscesses and 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 EP2 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. ONO-AE1-259, an EP2 receptor agonist, and rolipram, a phoshodiesterase type 4 inhibitor, reversed the effects of COX inhibitors on abscess formation. In contrast, 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. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19726696 |
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