IFN-alpha2b suppresses the fibrogenic effects of insulin-like growth factor-1 in dermal fibroblasts.
The interferon (IFN) proteins, including IFN-alpha2b have been used as antifibrogenic factors to modulate the expression of extracellular matrix (ECM) proteins associated with fibroproliferative disorders in skin. This study was conducted to determine if IFN-alpha2b can counteract the fibrogenic effects of insulin-like growth factor-1 (IGF-1), which is present in large quantity in fibrotic dermis. Human dermal fibroblasts were established in culture and treated with either vehicle (control), 2000 U/ml IFN-alpha2b alone, 100 ng/ml IGF-1 alone, or both IFN-alpha2b and IGF-1. The results showed that treatment with IFN-alpha2b inhibited the proliferation of dermal fibroblasts, reduced the steady-state levels of type I procollagen mRNA in the cells, and reduced the production of collagen as measured by hydroxyproline in conditioned medium. However, this treatment also increased levels of collagenase mRNA in the cells and collagenase activity in the medium. Cells treated with IGF-1 showed increased proliferation and collagen production and decreased collagenase. Cells treated with both IFN-alpha2b and IGF-1 exhibited a 44% reduction in hydroxyproline production (p < 0.05) and a 363% increase in collagenase activity over cells treated with IGF-1 alone (p < 0.01). These results indicate that when IGF-1 and IFN-alpha2b are used individually, they function as fibrogenic and antifibrogenic factors for dermal fibroblasts, respectively, and that fibrogenic effects of IGF-1 on cell proliferation, collagen, and collagenase expression can be counteracted by IFN-alpha2b. These findings support the potential use of IFN-alpha2b as a therapeutic agent for treatment of fibroproliferative disorders, such as postburn hypertrophic scarring.
Telasky
C
C
Department of Surgery, Wound Healing Research Group, University of Alberta, Edmonton, Canada.
Tredget
E E
EE
Shen
Q
Q
Khorramizadeh
M R
MR
Iwashina
T
T
Scott
P G
PG
Ghahary
A
A
D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000235:genetics; D017364:Collagenases / Q000235:genetics; D003864:Depression, Chemical; D020405:Dermis / Q000166:cytology / Q000187:drug effects*; D015536:Down-Regulation; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012333:RNA, Messenger; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D003094:Collagen; D017364:Collagenases