The mode of action of prostaglandin (PG) I1 analog, SM-10906, on fibroblasts of hypertrophic scars is similar to PGE1 in its potential role of preventing scar formation.
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.
Zhou
L J
LJ
Department of Dermatology, Fukushima Medical College, Japan.
Inoue
M
M
Ono
I
I
Kaneko
F
F
D000293:Adolescent; D000328:Adult; D000527:Alprostadil / Q000494:pharmacology*; D000933:Antifibrinolytic Agents / Q000378:metabolism; D002096:C-Peptide / Q000187:drug effects / Q000378:metabolism; D017439:Cicatrix, Hypertrophic / Q000188:drug therapy* / Q000517:prevention & control*; D003094:Collagen / Q000187:drug effects / Q000378:metabolism; D017364:Collagenases / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005341:Fibrinolysin / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000187:drug effects / Q000378:metabolism; D000979:alpha-2-Antiplasmin
D000933:Antifibrinolytic Agents; D002096:C-Peptide; D016207:Cytokines; D015850:Interleukin-6; D016209:Interleukin-8; D010975:Platelet Aggregation Inhibitors; C086699:SM 10906; D016212:Transforming Growth Factor beta; D000979:alpha-2-Antiplasmin; C037742:plasmin-plasmin inhibitor complex; D003094:Collagen; D011464:Epoprostenol; D000242:Cyclic AMP; D005341:Fibrinolysin; D017364:Collagenases; D000527:Alprostadil