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

Koh Ichi Yuhki, Fumitaka Ushikubi, Hiroaki Naraba, Akinori Ueno, Hirotsugu Kato, Fumiaki Kojima, Shuh Narumiya, Yukihiko Sugimoto, Misao Matsushita, Sachiko Oh-ishi

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    Abstract

    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) E2 (EP-/- mice) or PGI2 (IP-/- mice). Zymosan-induced exudate formation was significantly reduced in IP -/- mice compared with wild-type (WT) mice, whereas none of the EP-/- mice (EP1-/-, EP2 -/-, EP3-/-, and EP4-/- 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 PGI2 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 PGI2-IP system together with the complement system plays a key role in exudate formation in zymosan-induced pleurisy.

    Original languageEnglish (US)
    Pages (from-to)601-609
    Number of pages9
    JournalJournal of Pharmacology and Experimental Therapeutics
    Volume325
    Issue number2
    DOIs
    StatePublished - May 1 2008

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    ASJC Scopus subject areas

    • Molecular Medicine
    • Pharmacology

    Cite this

    Yuhki, K. I., Ushikubi, F., Naraba, H., Ueno, A., Kato, H., Kojima, F., Narumiya, S., Sugimoto, Y., Matsushita, M., & Oh-ishi, S. (2008). Prostaglandin I2 plays a key role in zymosan-induced mouse pleurisy. Journal of Pharmacology and Experimental Therapeutics, 325(2), 601-609. https://doi.org/10.1124/jpet.107.134494