Glucocorticoid-induced contractility and F-actin content of human lung fibroblasts in three-dimensional culture.
Fibroblast contractility plays a useful role in the wound healing process but contributes to architectural distortion in the lungs. Glucocorticoids (GCs) have been reported to reduce dermal fibroblast contractility, which may result in delaying wound healing, but the effects on lung fibroblasts are unknown. In this study, we examined how human lung fibroblast contractility is altered in the presence of GCs. Lung fibroblast cell lines (n = 5) were established from normal parts of surgically resected lung tissue. The effects of GCs on contractility were investigated with a type I collagen gel contraction assay. Filamentous actin (F-actin) content was detected by confocal microscopy and measured with a fluorescent phalloidin binding assay. GCs augmented fibroblast contraction in a concentration-dependent manner, with an approximate EC(50) of 1.8 x 10(-8) M, whereas other steroid derivatives had no effects. GC contractility needed de novo protein synthesis. The GC-induced increase in contractility was found to be consistent with an increase in F-actin content. In conclusion, lung fibroblast contractility was enhanced with GCs through an upregulation of lung fibroblast F-actin.
Miki
H
H
Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
Mio
T
T
Nagai
S
S
Hoshino
Y
Y
Tsutsumi
T
T
Mikuniya
T
T
Izumi
T
T
D000199:Actins / Q000378:metabolism*; D002478:Cells, Cultured; D002784:Cholesterol / Q000494:pharmacology; D003094:Collagen / Q000502:physiology; D003513:Cycloheximide / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D005782:Gels; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D013256:Steroids / Q000494:pharmacology
D000199:Actins; D005782:Gels; D005938:Glucocorticoids; D013256:Steroids; D003907:Dexamethasone; D003094:Collagen; D002784:Cholesterol; D003513:Cycloheximide