Cyclooxygenase in normal human tissues – is COX‐1 really a constitutive isoform, and COX‐2 an inducible isoform?

Abstract

Cyclooxygenase (COX) is a key enzyme in prostanoid synthesis. It exists in two isoforms, COX-1 and COX-2. COX-1 is referred to as a ‘constitutive isoform’, and is considered to be expressed in most tissues under basal conditions. In contrast, COX-2 is referred to as an ‘inducible isoform’, which is believed to be undetectable in most normal tissues, but can be up-regulated during various conditions, many of them pathological. Even though the role of COX in homeostasis and disease in now well appreciated, controversial information is available concerning the distribution of COX isoforms in normal human tissues. There is mounting evidence that it is much more complex than generally believed. Our aim was therefore to analyse the expression and distribution of COX isoforms in normal human tissues, using immunohistochemistry, Western blotting and real-time RT-PCR. Autopsy samples from 20 healthy trauma victims and samples from 48 biopsy surgical specimens were included. COX-1 was found in blood vessels, interstitial cells, smooth muscle cells, platelets and mesothelial cells. In contrast, COX-2 was found predominantly in the parenchymal cells of many tissues, with few exceptions, for example the heart. Our results confirm the hypothesis that the distribution of COX isoforms in healthy tissues is much more complex than generally believed. This and previous studies indicate that both isoforms, not only COX-1, are present in many normal human tissues, and that both isoforms, not only COX-2, are up-regulated in various pathological conditions. We may have to revise the concept of ‘constitutive’ and ‘inducible’ COX isoforms.

Immunohistochemical localisation of renal cyclooxygenase-1 expression in non-steroidal anti-inflammatory drug-treated mice

“…Of interest is the presence of COX-1 protein in the proximal convoluted tubule, a finding that has not previously been reported. COX-1 expression was also evident within the endothelial cells of the renal vasculature and the cortical and medullary collecting ducts which agree with previous reports (Vitzthum et al, 2002;Zidar et al, 2008). Immunohistochemical analysis revealed COX-A c c e p t e d m a n u s c r i p t 9 1 staining within the parietal epithelium of the Bowman's capsule.…”

“…Immunohistochemical analysis revealed COX-A c c e p t e d m a n u s c r i p t 9 1 staining within the parietal epithelium of the Bowman's capsule. This is in keeping with data from Zidar et al (2008) who localized COX-1 expression in the same area. However this study did not find COX-1 staining within the mesangium of the glomerulus.…”

“…Previous studies have documented the expression of COX-1 in human, rat and murine kidney (Campean et al, 2003;Khan et al, 1998;Komhoff et al, 1997;Vitzthum et al, 2002;Zidar et al, 2008). Human COX-1 protein expression was reported in the collecting duct cells, endothelial cells of the renal vasculature (moreso in the afferent arteriole at the glomerular entrance), interstitial cells and in the parietal cells of Bowman's capsule (Komhoff et al, 1997).…”

Cyclooxygenases: structural and functional insights

“…Although more highly variable, COX-2 protein was found in nearly all tissues and was most often localized to parenchymal cells (13). Constitutive COX-2 expression is well recognized in brain, kidney, and the female reproductive tract, and evidence for induction of COX-1 during the lipopolysaccharide (LPS)-mediated inflammatory response and cellular differentiation has been reported (14)(15)(16)(17)(18).…”

Ethyl cellulose nanoparticles as a platform to decrease ulcerogenic potential of piroxicam: formulation and in vitro/in vivo evaluation

“…In the same context, it has been suggested that the anti-inflammatory actions of NSAIDs are induced by the inhibition of COX-2, while their adverse effects of ulceration are precipitated by the over-inhibition of COX-1. 3 Another contributing factor to gastric side effects of NSAIDs is their local action. NSAIDs are reported to remain in crystalline form in the acidic medium of the stomach.…”