Expression and role of cyclooxygenase isoforms in alveolar and peritoneal macrophages

Abstract

Prostaglandin synthesis represents one means by which macrophages modulate inflammation. The initial enzyme in the metabolism of arachidonic acid to prostaglandins is cyclooxygenase (COX). Both constitutive (COX-1) and inducible (COX-2) isoforms are recognized. We previously showed that COX activity of rat peritoneal macrophages (PM) exceeds that of alveolar macrophages (AM). In this study, we correlated the steady-state levels of COX-1 and COX-2 proteins with COX activity in resident AM and PM. Freshly obtained AM contained lower levels of COX-1 than did fresh PM. Neither contained substantial amounts of COX-2 in the basal state, but both cell types demonstrated induction when cultured with lipopolysaccharide; once again, COX-2 levels in PM exceeded those in AM. Despite COX-2 induction under these circumstances, its contribution to prostaglandin production appeared to be modest. We conclude that, although both isoforms of COX are expressed in rat AM and PM, COX-1 is responsible for the majority of enzyme activity in both the basal and stimulated states. The lesser prostaglandin synthetic capacity of AM than of PM appears to be the consequence of lower steady-state levels of both COX proteins.

Calcium/calmodulin‐dependent protein kinase II regulates cyclooxygenase‐2 expression and prostaglandin E2 production by activating cAMP‐response element‐binding protein in rat peritoneal macrophages

“…30 Among these factors, PGE 2 is one of the most important, which is also linked to the progress of tumours. 31 Because COX-2 expression is controlled by the c/EBPb and CREB signalling pathways in macrophage cell line 20 and Ca…”

Chemotactic action of prostaglandin E2on mouse mast cells acting via the PGE2receptor 3

“…More recent studies showed the synthesis of PGE 2 by epithelial and stromal cells, and increased cyclooxygenase-2 expression in intestinal myofibroblasts (38,39). In the lung, PGE 2 is principally synthesized by three cell types, epithelial cells (40,41), macrophages (42), and fibroblasts (43).…”

Inhibition of IL-10 Receptor Function in Alveolar Macrophages by Toll-Like Receptor Agonists

“…However, the ability of these factors to regulate inflammation in normal lung depends on their presence and activity during homeostatic conditions. In this regard, the levels of PGE 2 and TGF␤ in normal lung are quite low and most of the TGF␤ in normal lung is present in its latent form (24,25). NO production by AM has been proposed to be largely responsible for the regulation of lymphocyte activity in the lung (23,26).…”