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Dermal fibroblasts are one of the therapeutic targets for topical application of 1α,25‐dihydroxyvitamin D 3 : the possible involvement of transforming growth factor‐β induction
Author(s) -
Oyama N.,
Iwatsuki K.,
Satoh M.,
Akiba H.,
Kaneko F.
Publication year - 2000
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1046/j.1365-2133.2000.03880.x
Subject(s) - transforming growth factor , growth factor , medicine , cancer research , dermatology , receptor
Background Transforming growth factor (TGF) ‐β has been suggested to be an effective inhibitor for abnormal keratinocyte growth in psoriasis. As a majority of the secreted TGF‐β are biologically latent complexes, activation is essential for TGF‐β‐mediated cellular responses in vitro and in vivo . Objectives Here we report the response of the TGF‐β regulation system to 1α,25‐dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ], an active vitamin D 3 analogue Patients/methods We studied two types of fibroblasts derived from normal and psoriatic lesional skin, using an enzyme‐linked immunosorbent assay and Northern blotting techniques. Results 1,25(OH) 2 D 3 caused a dose‐dependent induction of latent and active TGF‐β1 proteins in both cell cultures. The increases were significant over 72 h, but not within 48 h after stimulation. The time course of TGF‐β1 mRNA expression showed a biphasic response consisting of early (≈1 h) and late phases (≈ 96 h) of induction. Concomitant increases of TGF‐β2 and ‐β3, other mammalian isoforms, were observed in the 1,25(OH) 2 D 3 ‐treated cells, but the kinetics were all different. Co‐incubation with metabolic inhibitors, actinomycin D and cycloheximide, revealed that the early induction of TGF‐β1 mRNA by 1,25(OH) 2 D 3 is dependent on de novo RNA synthesis, but not on RNA stabilization or protein synthesis. It seems likely to be a transient and negligible response given the absence of TGF‐β1 protein production. The late induction of TGF‐β1 mRNA was partially blocked by adding isoform‐specific antibodies to TGF‐β1, ‐β2 and ‐β3, indicating TGF‐β autoregulation. Despite these marked responses, there were no significant differences in the TGF‐β expression between normal and psoriatic fibroblasts. Conclusions These results suggest that antiproliferative and anti‐inflammatory effects of 1,25(OH) 2 D 3 on psoriatic lesional skin may be mediated, at least in part, by a complex TGF‐β regulation in local dermal fibroblasts.