Expression of cyclooxygenase isoforms in normal human skin and chronic venous ulcers.
Chronic venous ulcers are an example of abnormal wound healing showing chronic inflammation which together with the underlying vascular pathology results in delayed healing. Prostaglandins are among the most important mediators of inflammation. They have proinflammatory effects, predominantly by affecting the vasculature. Cyclooxygenase (COX) is the rate-limiting enzyme in prostanoid synthesis. It is present in two isoforms: COX-1 (constitutive cyclooxygenase) which is produced in the body to maintain normal haemostatic functions, and COX-2 (inducible cyclooxygenase), which is induced during inflammation in response to cytokines. Using immunoenzymatic labelling and western blot analysis, this study has shown that both COX-1 and COX-2 were up-regulated in chronic venous leg ulcers by comparison with normal human skin. De novo appearance of COX-2 in chronic venous ulcers was demonstrated, which is not seen in normal human skin. The main cellular sources of both COX isoforms are macrophages and endothelial cells. COX-2 is also produced by mast cells and fibroblasts. A COX radioimmunoassay showed up-regulation of COX activity in chronic venous ulcers compared with normal skin (p<0.05). Up-regulation of COX-1 in chronic venous leg ulcers could produce prostacyclin, which contributes to angiogenesis. Thus, inhibition of COX-1 by non-steroidal anti-inflammatory drugs (NSAIDs) could increase the local ischaemia and hypoxia associated with chronic venous ulcers. On the other hand, up-regulation of COX-2 is most likely responsible for the persistent inflammation in chronic venous leg ulcers. COX-2 selective inhibitors could therefore be effective in the treatment of chronic venous ulcers.
Abd-El-Aleem
S A
SA
School of Biological Sciences, University of Manchester, Room 3.239, Stopford Building, Oxford Road, Manchester M13 9PT, UK.
Ferguson
M W
MW
Appleton
I
I
Bhowmick
A
A
McCollum
C N
CN
Ireland
G W
GW
D015153:Blotting, Western; D002908:Chronic Disease; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D006801:Humans; D007124:Immunoenzyme Techniques; D007527:Isoenzymes / Q000378:metabolism*; D008264:Macrophages / Q000201:enzymology; D008565:Membrane Proteins; D008875:Middle Aged; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D012867:Skin / Q000201:enzymology*; D014647:Varicose Ulcer / Q000201:enzymology*
D007527:Isoenzymes; D008565:Membrane Proteins; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases