c-peptide and Cicatrix--Hypertrophic

To investigate the role of prostaglandin (PG) E1 in preventing scar formation as well as that of the related cytokines, we culture fibroblasts from hypertrophic scar tissue (SDF) and normal dermis (NDF) collected from patients with scar contracture. We have compared the type I collagen synthesis, type I collagenase activity, and the production of interleukin (IL)-6, IL-8 and transforming growth factor (TGF)-beta(1) in two types of cultured fibroblasts before and after addition of PGE1. Our results demonstrated that levels of type I collagen and TGF-beta(1) production were higher and that type I collagenase activity and IL-8 production were significantly lower in the culture supernatants of SDF. There was no significance difference in IL-6 production between SDF and NDF culture supernatants. On the other hand, PGE1 significantly increased type I collagenase activity and IL-8 production in the SDF culture supernatants and it increased IL-6 and TGF-beta(1) production in both types of fibroblasts. However, there was no effect on synthesis of type I collagen in either group. To further investigate the role of TGF-beta(1) in NDF and SDF, exogenous recombinant human (rh) TGF-beta(1) was added. In NDF group, rhTGF-beta(1) induced a decrease in the type I collagenase/type I collagen ratio, while rhTGF-beta(1) had no effect on the same ratio in the SDF group. These results suggest that PGE1 may have a role in the prevention of hypertrophic scar by increasing the activity of type I collagenase.

Topics: Adolescent; Adult; Alprostadil; C-Peptide; Cells, Cultured; Cicatrix, Hypertrophic; Collagenases; Cytokines; Extracellular Matrix; Female; Fibroblasts; Humans; Interleukin-6; Interleukin-8; Male; Recombinant Proteins; Skin; Transforming Growth Factor beta

The effects of prostaglandin (PG) I1 analog, SM-10906 (SM-6) and PGE1 on extracellular matrix formation and the release of cytokines by cultured normal human dermal fibroblasts (NDF) and hypertrophic scar fibroblasts (HSF) were compared in order to evaluate the clinical efficacy of PGs in preventing scar formation. In the present study, we measured type I collagen synthesis, collagenase activity, production of interleukin (IL)-6, IL-8, and transforming growth factor (TGF)-beta 1 and levels of adenosine 3,5-cyclic monophosphate (cAMP) in NDF and HSF cultured with or without PGs. The results demonstrated that HSF culture supernatants has a significantly higher level of type I collagen and TGF-beta 1 than those of NDF. However, the levels of collagenase activity and IL-8 in HSF were significantly lower in comparison to that of NDF. There was no substantial difference in IL-6 production between two types of culture cells. On the other hand, PGE1 and SM-6 significantly enhanced collagenase activity and raised the collagenase/type I collagen ratio in the HSF supernatants. In addition, both PGE1 and SM-6 increased production of TGF-beta 1, IL-8 and IL-6 and levels of cAMP in both cell types. However, they had no effect on the type I collagen synthesis of either types. These results suggest that, the stable PGI1 analog, SM-6, similarly acts as PGE1 in HSF by increasing the activity of collagenase.

Topics: Adolescent; Adult; alpha-2-Antiplasmin; Alprostadil; Antifibrinolytic Agents; C-Peptide; Cicatrix, Hypertrophic; Collagen; Collagenases; Cyclic AMP; Cytokines; Dose-Response Relationship, Drug; Epoprostenol; Extracellular Matrix; Female; Fibrinolysin; Fibroblasts; Humans; Interleukin-6; Interleukin-8; Male; Platelet Aggregation Inhibitors; Transforming Growth Factor beta