Cyclooxygenase-2 expression during allergic inflammation in guinea-pig lungs

Tsuyoshi Oguma, Koichiro Asano, Tetsuya Shiomi, Kouichi Fukunaga, Yusuke Suzuki, Morio Nakamura, Hiroaki Matsubara, Holly K. Sheldon, Kathleen J. Haley, Craig M. Lilly, Jeffrey M. Drazen, Kazuhiro Yamaguchi

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36 Citations (Scopus)

Abstract

Prostaglandins and thromboxanes are important modulators of airway physiology. The synthesis of these mediators depends on two isoforms of cyclooxygenase (COX), constitutive COX-1 and inducible COX-2. COX-2 expression has been observed in various inflammatory diseases, but not all aspects of the expression and the role of COX-2 in conditions of allergic inflammation such as asthma are clear. In the present study, we examined the 72-h kinetics of the expression of COX-isoform mRNA in ovalbumin-sensitized and -challenged guinea-pig lungs. The sensitized animals showed a robust and transient induction of COX-2 mRNA expression within 1 h after ovalbumin challenge, whereas their COX-1 mRNA levels remained unchanged. Upregulation of the level and activity of COX-2 protein followed the induction of COX-2 mRNA. Lung slices harvested from ovalbumin-challenged animals released more prostaglandin D2 and prostaglandin E2 spontaneously or in response to A23187 (10 μM) ex vivo than did those from unchallenged animals. This response was significantly blocked by the COX-2 selective inhibitors, NS-398 and JTE-522. In vivo administration of NS-398 significantly inhibited the accumulation of eosinophils and neutrophils in the lungs. In conclusion, de novo COX-2 expression during allergic inflammation modifies prostanoid synthesis in the lung and airway pathophysiology.

Original languageEnglish
Pages (from-to)382-386
Number of pages5
JournalAmerican journal of respiratory and critical care medicine
Volume165
Issue number3
DOIs
Publication statusPublished - 2002 Feb 1

Keywords

  • Asthma
  • Cyclooxygenase inhibitors
  • Prostaglandin
  • Thromboxane

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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    Oguma, T., Asano, K., Shiomi, T., Fukunaga, K., Suzuki, Y., Nakamura, M., Matsubara, H., Sheldon, H. K., Haley, K. J., Lilly, C. M., Drazen, J. M., & Yamaguchi, K. (2002). Cyclooxygenase-2 expression during allergic inflammation in guinea-pig lungs. American journal of respiratory and critical care medicine, 165(3), 382-386. https://doi.org/10.1164/ajrccm.165.3.2103093