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

1 We characterized the regulation of cyclooxygenase-2 (COX-2) at the mRNA, protein and mediator level in two rat models of acute inflammation, carrage enan-induced paw oedema and mechanical hyperalgesia. 2 Carrageenan was injected in the hind paw of rat at low (paw oedema) and h igh doses (hyperalgesia). COX-2 and prostaglandin E-2 (PGE(2)) levels were measured by RT-PCR and immunological assays. We also determined the distrib ution of COX-2 by immunohistochemistry. 3 The injection of carrageenan produced a significant and parallel inductio n of both COX-2 and PGE(2). This induction was significantly higher in hype ralgesia than in paw oedema. This was probably due to the 9 fold higher con centration of carrageenan used to provoke hyperalgesia. 4 Immunohistochemical examination showed COX-2 immunoreactivity in the epid ermis, skeletal muscle and inflammatory cells of rats experiencing hyperalg esia. In paw oedema however, only the epidermis showed positive COX-2 immun oreactivity. 5 Pretreatment with indomethacin completely abolished the induction of COX- 2 in paw oedema but not in hyperalgesia. 6 These results suggest that multiple mechanisms regulate COX-2 induction e specially in the more severe model. In carrageenan-induced paw oedema, pros tanoid production have been linked through the expression of the COX-2 gene which suggest the presence of a positive feedback loop mechanism.