Expression of cyclooxygenase isoforms in normal human skin and chronic venous ulcers

Abstract

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.

Effect of Chunghyuldan in Chronic Oxazolone-Induced Mouse Dermatitis

“…9) This dermatitis was accompanied by sustained swelling, predominant epidermal hyperplasia and marked infiltration of inflammatory cells consisting of monocytes, granulocytes and macrophages, but not eosionphils. In the present study, the oxazolone-induced dermatitis was also accompanied by substained swelling and predominant epidermal hyperplasia as reported by Fujii et al 9) IFN-g and TNF-a, which are cytokines involved in chronic skin inflammatory disease, [14][15][16] and COX-2, which is an acute marker of acute inflammatory disease were induced. CHD, which is a potent inhibitor against NO and PGE2 productions in LPS-induced RAW264.7 cells, 12) significantly inhibited sustained swelling (thickness) of mice ear induced by oxazolone as well as mRNA levels of COX-2.…”

Biological Impact of Melatonin on the Healing of Albino Rats’ Tongue Ulcer.

“…Endothelial cells proliferate and migrate during new blood vessel formation and new vessels provide nutrients and oxygen to the newly formed tissue. These events are known to be initiated and driven by various growth factors especially VEGF165, the biologically active and most potent angiogenic protein known (21) . During normal wound healing, new blood vessel formation is initiated on day 3, peaks at day 7 and is essential for the formation of granulation tissue (22) .…”

Anti-inflammatory potential of peat moss extracts in lipopolysaccharide-stimulated RAW 264.7 macrophages

“…The inducible enzymes (iNOS and COX-2) and their reaction products are associated with inflammatory diseases. Both enzymes are upregulated in the inflammatory response, and their reactive products, NO and PGE 2 , respectively, are closely related to various chronic diseases, such as ulcers and RA (18,19). TNF-α and IL-1β secreted from activated monocytes and macrophages exerts a vareity of pro-inflammatory effects on many cell types (20).…”