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

Abstract

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.

Stimulatory effects of dibutyryl cyclic adenosine monophosphate on cytokine production by keratinocytes and fibroblasts

“…The harvested fibroblasts were transferred to a 25‐cm 3 culture flask (Falcon; Becton Dickinson) and subcultured in 10% FBS/DMEM. Subsequent subcultures were performed according to procedures reported previously 3,9 , 10 . Fibroblasts from passages 3–5 were used in the experiments.…”

“…Cell proliferation was measured 10–12 by the 5‐bromodeoxyuridine (BrdU) incorporation method using a BrdU detection kit (Boehringer Mannheim Biochemical, Mannheim, Germany) according to the manufacturer's instructions. In brief, fibroblasts or keratinocytes were seeded on 96‐well plates and BrdU‐labelling solution was added to the plates 6 h before measurement.…”

Nonsteroidal Anti-Inflammatory Drugs for Wounds: Pain Relief or Excessive Scar Formation?

“…Besides, PGE2, PGE1, and its analog can increase the activity of collagenase, which is lower in the supernatants from hypertrophic scar fibroblasts culture [40]. PGE1 may have a role in the prevention of hypertrophic scarring by increasing the activity of type I collagenase [29].…”

Stimulatory effects of dibutyryl cyclic adenosine monophosphate on cytokine production by keratinocytes and fibroblasts

“…Subsequent subcultures were performed according to procedures reported previously. 3,9,10 Fibroblasts from passages 3±5 were used in the experiments.…”