Cyclooxygenase-2 participates in the late phase of airway hyperresponsiveness after ozone exposure in guinea pigs

Hiroyuki Nakano, Hisamichi Aizawa, Koichiro Matsumoto, Satoru Fukuyama, Hiromasa Inoue, Nobuyuki Hara

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Abstract

We examined the role of cyclooxygenase in airway hyperresponsiveness and inflammation after ozone exposure in guinea pigs using a non-selective (indomethacin) and a selective (JTE-522) cyclooxygenase-2 inhibitor. Spontaneously breathing guinea pigs were exposed to ozone (3 ppm) for 2 h after treatment with vehicle, indomethacin (10 mg/kg) or JTE-522 (10 mg/kg). Airway responsiveness to inhaled histamine (PC200) and bronchoalveolar lavage were assessed before, immediately and 5 h after ozone exposure. Ozone caused a significant airway hyperresponsiveness immediately after exposure, which persisted after 5 h. Neither JTE-522 nor indomethacin affected airway hyperresponsiveness immediately after ozone exposure, but significantly attenuated airway hyperresponsiveness 5 h after exposure, suggesting that cyclooxygenase-2 may participate in the late phase of airway hyperresponsiveness but not in the early phase. Ozone caused a significant increase in the concentration of prostaglandin E2 and thromboxane B2 in bronchoalveolar lavage fluid immediately after exposure, which decreased to the basal level 5 h after exposure. This increase in prostaglandin E2 and thromboxane B2 was significantly inhibited by JTE-522. An expression of cyclooxygenase-2 was detected not only after ozone exposure but also before, and there was no difference in the number of cyclooxygenase-2-positive cells at any time point. An exogenously applied thromboxane A2 mimetic, U-46619 (10-5 M), induced airway hyperresponsiveness 5 h after inhalation, but not immediately or 3 h after inhalation. These data suggest that cyclooxygenase-2 may be constitutively expressed before ozone exposure in guinea pig airway and may synthesize prostaglandin E2 and thromboxane A2 transiently under ozone stimulation and that thromboxane A2 may, in turn, induce the late phase of airway hyperresponsiveness. (C) 2000 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)267-275
Number of pages9
JournalEuropean Journal of Pharmacology
Volume403
Issue number3
DOIs
Publication statusPublished - Jan 1 2000

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All Science Journal Classification (ASJC) codes

  • Pharmacology

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