Effects of mometasone furoate on human keratinocytes and fibroblasts in vitro.
The long-term treatment of inflammatory skin diseases with topical glucocorticoids is limited by their side effects such as skin atrophy, delayed wound healing and striae distensae. Mometasone furoate (MF) is a newly synthesized glucocorticoid with the advantage of increasing efficacy and reducing the number of adverse effects. The aim of our study was to compare the effects of MF and conventional fluorinated corticosteroids on a human keratinocyte cell line (HaCat) and human skin fibroblasts in vitro. Monolayer cultures of these cell lines were exposed to different concentrations of the active compounds for 5 days to analyze the influence on morphology and proliferation. Chemotaxis of HaCat cells and fibroblasts was studied in blind-well Boyden chambers using collagen type I and fibroblast-conditioned medium as a chemoattractant. Additionally, fibroblasts were used to investigate the contraction of collagen gels since lattice contraction appears to model the contraction of skin wounds. All glucocorticoids tested influenced fibroblast and keratinocyte proliferation in a dose-dependent manner, yet the effect was clearly more marked with fluorinated corticosteroids than with MF. Similar effects were obtained using the chemotaxis assay. At low concentrations (10(-9) M) MF exerted almost no influence, while the conventional fluorinated substances inhibited direct migration significantly. Contraction of collagen gels was inhibited completely by betamethasone valerate at high concentrations (10(-5)-10(-3) M), but only partially inhibited by MF at its highest concentration (10(-3) M). Although MF reveals high anti-inflammatory activity similar to that known for conventional fluorinated derivatives of corticosteroids, the study shows that MF has less effect in the tested in vitro systems. Therefore, it remains to be seen whether these data might indicate the possibility of a dissociation between the inflammatory activity and the inhibition of the biosynthetic capacities of fibroblasts and keratinocytes by modification of the steroidal structure of corticosteroids.
Wach
F
F
Department of Dermatology, University of Regensburg, Germany.
Bosserhoff
A
A
Kurzidym
U
U
Nowok
K
K
Landthaler
M
M
Hein
R
R
D000287:Administration, Topical; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects; D005782:Gels; D005938:Glucocorticoids; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects*; D000068656:Mometasone Furoate; D011244:Pregnadienediols / Q000494:pharmacology*; D012867:Skin / Q000166:cytology / Q000187:drug effects*
D000893:Anti-Inflammatory Agents; D005782:Gels; D005938:Glucocorticoids; D011244:Pregnadienediols; D000068656:Mometasone Furoate; D003094:Collagen