Inducible cyclooxygenase may have anti-inflammatory properties

DW Gilroy, PR Colville-Nash, D Willis, J Chivers… - Nature medicine, 1999 - nature.com
DW Gilroy, PR Colville-Nash, D Willis, J Chivers, MJ Paul-Clark, DA Willoughby
Nature medicine, 1999nature.com
Cyclooxygenase (COX) has two isoforms. Generally, COX 1 is constitutively expressed in
most tissues, where it maintains physiological processes 1; inducible COX 2 is considered a
pro-inflammatory enzyme and a chief target for the treatment of inflammatory diseases 2.
Here we present evidence that COX 2 may have anti-inflammatory properties. In
carrageenin-induced pleurisy in rats, the predominant cells at 2 hours are
polymorphonuclear leucocytes, whereas mononuclear cells dominate from 24 hours until …
Abstract
Cyclooxygenase (COX) has two isoforms. Generally, COX 1 is constitutively expressed in most tissues, where it maintains physiological processes 1; inducible COX 2 is considered a pro-inflammatory enzyme and a chief target for the treatment of inflammatory diseases 2. Here we present evidence that COX 2 may have anti-inflammatory properties. In carrageenin-induced pleurisy in rats, the predominant cells at 2 hours are polymorphonuclear leucocytes, whereas mononuclear cells dominate from 24 hours until resolution at 48 hours 3. In this model, COX 2 protein expression peaked initially at 2 hours, associated with maximal prostaglandin E 2 synthesis. However, at 48 hours there was a second increase in COX 2 expression, 350% greater than that at 2 hours. Paradoxically, this coincided with inflammatory resolution and was associated with minimal prostaglandin E 2 synthesis. In contrast, levels of prostaglandin D 2, and 15deoxyΔ 12, 13, 14 prostaglandin J 2 were high at 2 hours, decreased as inflammation increased, but were increased again at 48 hours. The selective COX 2 inhibitor NS-398 and the dual COX 1/COX 2 inhibitor indomethacin inhibited inflammation at 2 hours but significantly exacerbated inflammation at 48 hours. This exacerbation was associated with reduced exudate prostaglandin D 2 and 15deoxyΔ 12, 13, 14 prostaglandin J 2 concentrations, and was reversed by replacement of these prostaglandins. Thus, COX 2 may be pro-inflammatory during the early phase of a carrageenin-induced pleurisy, dominated by polymorphonuclear leucocytes, but may aid resolution at the later, mononuclear cell-dominated phase by generating an alternative set of anti-inflammatory prostaglandins.
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