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Distribution and regulation of cyclooxygenase‐2 in carrageenan‐induced inflammation
Author(s) -
Nantel François,
Denis Danielle,
Gordon Robert,
Northey Angela,
Cirino Maria,
Metters Kathleen M,
Chan Chi Chung
Publication year - 1999
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0702866
Subject(s) - cyclooxygenase , hyperalgesia , carrageenan , inflammation , chemistry , eicosanoid , prostaglandin , prostaglandin e2 , prostaglandin e , epidermis (zoology) , pharmacology , endocrinology , medicine , biochemistry , nociception , anatomy , enzyme , receptor , arachidonic acid
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 E 2 (PGE 2 ) 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 PGE 2 . 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