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J Pharmacol Exp Ther. 2008 May;325(2):601-9. doi: 10.1124/jpet.107.134494. Epub 2008 Feb 6.

Prostaglandin I2 plays a key role in zymosan-induced mouse pleurisy.

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Department of Pharmacology, Asahikawa Medical College, 2-1-1-1 Midorigaoka-Higashi, Asahikawa 078-8510, Japan.


Zymosan, the cell wall of Saccharomyces cerevisiae, induces innate immune responses involving prostanoid production and complement activation. However, the roles of prostanoids in zymosan-induced inflammation and their interaction with the complement system remain to be determined. To clarify these issues, we examined zymosan-induced pleurisy in mice lacking receptors for prostaglandin (PG) E(2) (EP(-/-) mice) or PGI(2) (IP(-/-) mice). Zymosan-induced exudate formation was significantly reduced in IP(-/-) mice compared with wild-type (WT) mice, whereas none of the EP(-/-) mice (EP(1)(-/-), EP(2)(-/-), EP(3)(-/-), and EP(1)(-/-)(4) mice) showed any significant difference from WT mice. Furthermore, indomethacin, an inhibitor of prostanoid biosynthesis, suppressed exudate formation in WT mice to almost the same level as that of IP(-/-) mice. Accordingly, significant production of PGI(2) in the pleural cavity, suggested to be cyclooxygenase-2-dependent, was observed after zymosan injection. Complement activation in the pleural cavity after zymosan injection was confirmed, and preinjection of cobra venom factor (CVF), to deplete blood complement C3, was significantly suppressed after zymosan-induced exudate formation in WT mice. Simultaneous treatment with indomethacin and CVF further suppressed exudate formation in WT mice compared with each treatment alone. Because, some degree of exudate formation was still observed, other factor(s) seem to be involved. However, platelet-activating factor, a promising candidate as one such factor, was not involved in zymosan-induced exudate formation. These results clearly indicate that the PGI(2)-IP system together with the complement system plays a key role in exudate formation in zymosan-induced pleurisy.

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