Distribution and regulation of cyclooxygenase‐2 in carrageenan‐induced inflammation

British Journal of Pharmacology - Tập 128 Số 4 - Trang 853-859 - 1999
F. Nantel1, Danielle Denis1, Robert J. Gordon2, Angela Northey1, M. Cirino2, Kathleen M. Metters1, Chi Chung Chan2
1Department of Biochemistry and Molecular Biology, Merck Frosst Center for Therapeutic Research, P.O. Box 1005, Dorval–Pointe–Claire, Québec, H9R 4P8, Canada
2Department of Pharmacology, Merck Frosst Center for Therapeutic Research, P.O. Box 1005, Dorval‐Pointe‐Claire, Québec, H9R 4P8, Canada

Tóm tắt

We characterized the regulation of cyclooxygenase‐2 (COX‐2) at the mRNA, protein and mediator level in two rat models of acute inflammation, carrageenan‐induced paw ædema and mechanical hyperalgesia. Carrageenan was injected in the hind paw of rat at low (paw ædema) and high doses (hyperalgesia). COX‐2 and prostaglandin E2 (PGE2) levels were measured by RT–PCR and immunological assays. We also determined the distribution of COX‐2 by immunohistochemistry. The injection of carrageenan produced a significant and parallel induction of both COX‐2 and PGE2. This induction was significantly higher in hyperalgesia than in paw ædema. This was probably due to the 9 fold higher concentration of carrageenan used to provoke hyperalgesia. Immunohistochemical examination showed COX‐2 immunoreactivity in the epidermis, skeletal muscle and inflammatory cells of rats experiencing hyperalgesia. In paw ædema however, only the epidermis showed positive COX‐2 immunoreactivity. Pretreatment with indomethacin completely abolished the induction of COX‐2 in paw ædema but not in hyperalgesia. These results suggest that multiple mechanisms regulate COX‐2 induction especially in the more severe model. In carrageenan‐induced paw ædema, prostanoid production have been linked through the expression of the COX‐2 gene which suggest the presence of a positive feedback loop mechanism. British Journal of Pharmacology (1999) 128, 853–859; doi:10.1038/sj.bjp.0702866

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British Journal of Pharmacology

Tập 128 Số 4

853-859

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