Differential effects of hexoses and sucrose, and platelet-derived growth factor isoforms on cyclooxygenase-1 and -2 mRNA expression in keloid, hypertrophic scar and granulation tissue fibroblasts.
Cyclooxygenase (COX) is the key enzyme in the formation of prostaglandins in inflammation. In the present study the effects of biomedically relevant hexose sugars (glucose, fructose, galactose, mannose) and sucrose disaccharide on the expression of COX-1 and COX-2 genes were evaluated in granulation tissue fibroblasts, hypertrophic scar fibroblasts and keloid fibroblasts. The effects of three isoforms (AA, AB and BB) of PDGF on COX gene expression in granulation tissue fibroblasts were also examined. All cell lines expressed COX-1 mRNA, whilst fibroblasts derived from abnormal scars did not express COX-2 mRNA. COX-1 mRNA expression was decreased by sugars in granulation tissue fibroblasts and increased in hypertrophic scar fibroblasts. No major changes were seen in keloid fibroblasts. On the other hand, COX-2 mRNA expression in granulation tissue fibroblasts was decreased dramatically in the presence of fructose, mannose and sucrose and moderately in the presence of galactose. All isoforms of PDGF increased COX-1 and COX-2 mRNA expression in granulation tissue fibroblasts, the most marked increases being elicited by PDGF-BB. All fibroblast cell lines studied expressed the COX-1 gene while the COX-2 gene was not expressed by abnormal scar-derived fibroblasts. Further, granulation tissue fibroblasts seemed to behave differently under the influence of sugars compared to hypertrophic scar fibroblasts whilst keloid fibroblasts seemed to be relatively unaffected by sugars. In addition, the PDGF-BB isoform is a potent inducer of COX-2 gene expression in wound fibroblasts. These findings may be relevant to the development of abnormal scars and indicate the need for further studies.
Kössi
J
J
Department of Surgery, University of Turku, Kiinamyllynkatu 4-8, 20520 Turku, Finland.
Peltonen
J
J
Uotila
P
P
Laato
M
M
D002478:Cells, Cultured; D017439:Cicatrix, Hypertrophic / Q000378:metabolism* / Q000473:pathology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006097:Granulation Tissue / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006601:Hexoses / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007627:Keloid / Q000378:metabolism* / Q000473:pathology; D008565:Membrane Proteins; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D013395:Sucrose / Q000494:pharmacology*
D006601:Hexoses; D007527:Isoenzymes; D008565:Membrane Proteins; D010982:Platelet-Derived Growth Factor; D020033:Protein Isoforms; D012333:RNA, Messenger; D013395:Sucrose; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases