Human recombinant interleukin-1 beta up-regulates elastin gene expression in dermal fibroblasts. Evidence for transcriptional regulation in vitro and in vivo.
The effects of human recombinant interleukin (IL)-1 beta on elastin gene expression were studied in human skin fibroblast cultures by Northern hybridization and transient transfection experiments. Incubation of the cells with IL-1 beta elevated the elastin mRNA steady-state levels by approximately 3- to 4-fold. A similar increase was noted at the protein level, when estimated by indirect immunofluorescence of cultured cells. This effect was independent of the on-going protein synthesis, as tested by incubation with cycloheximide. Transient transfections of the dermal fibroblasts with a human elastin promoter/chloramphenicol acetyltransferase (CAT) reporter gene construct suggested transcriptional regulation, since the CAT activity in cells incubated with IL-1 beta was similarly increased approximately 3-fold. Enhancement of the human elastin promoter activity by IL-1 beta was also noted in fibroblast cultures established from the skin and lungs of transgenic mice which have integrated the human promoter/CAT construct into their genome and express it in a tissue-specific manner. Furthermore, subcutaneous injection of IL-1 beta to the mice resulted in a approximately 4-fold elevation of the CAT activity in the skin after a 30-h incubation, as compared to the CAT activity in the skin of control animals. Collectively, these data indicate that IL-1 beta up-regulates elastin gene expression in fibroblast cultures as well as in the skin in vivo, and the activation occurs at the transcriptional level.
Mauviel
A
A
Department of Dermatology, Jefferson Medical College, Philadelphia, Pennsylvania 19107.
Chen
Y Q
YQ
Kähäri
V M
VM
Ledo
I
I
Wu
M
M
Rudnicka
L
L
Uitto
J
J
D000818:Animals; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D004549:Elastin / Q000235:genetics* / Q000378:metabolism; D005347:Fibroblasts; D005786:Gene Expression Regulation; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology*; D051379:Mice; D011401:Promoter Regions, Genetic; D012867:Skin / Q000166:cytology / Q000378:metabolism; D014158:Transcription, Genetic; D015854:Up-Regulation
D007375:Interleukin-1; D004549:Elastin; D003513:Cycloheximide