Improved scar in postburn patients following interferon-alpha2b treatment is associated with decreased angiogenesis mediated by vascular endothelial cell growth factor.
Hypertrophic scar (HTS) after thermal injury is a dermal fibroproliferative disorder, which leads to considerable morbidity. Previous clinical studies from our laboratory have suggested that interferon-alpha2b (IFN-alpha2b) improves scar quality as a result of the suppression of fibroblast function. More recently, our work has demonstrated that the improvement of scar in patients with HTS after IFN-alpha2b treatment may be associated with a decreased number of fibrocytes and/or altered fibrocyte function. In this study, we report that the improvement of HTS after IFNalpha-2b treatment may be associated with a decrease in angiogenesis. Using immunohistochemistry, we demonstrate an increase in angiogenesis in HTS compared to normal skin, and also show an increase in the expression of vascular endothelial cell growth factor (VEGF) in HTS. Subsequently, we demonstrate a significant reduction in angiogenesis in HTS tissue from patients after treatment with systemic IFN-alpha2b. By using a [3H] thymidine incorporation assay, we demonstrate that IFN-alpha2b suppresses the proliferation of human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner. In addition, IFN-alpha2b inhibits VEGF-induced proliferation and tube formation by using HUVECs. All these effects may be a result of the blocking of VEGF receptor expression on endothelial cells by IFN-alpha2b. Taken together with previous results, the present study suggests that the improvement of scar quality in HTS patients after IFN-alpha2b treatment may also be associated with decreased angiogenesis in HTS. The current in vitro results may provide some insights into the scar improvement that is seen with systemic IFN-alpha2b treatment.
Wang
Jianfei
J
Wound Healing Research Group, Division of Plastic and Reconstructive Surgery, Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
Chen
Hong
H
Shankowsky
Heather A
HA
Scott
Paul G
PG
Tredget
Edward E
EE
D000293:Adolescent; D000328:Adult; D002056:Burns / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002648:Child; D017439:Cicatrix, Hypertrophic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000473:pathology; D011994:Recombinant Proteins; D012867:Skin / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2