Premium
Leukoregulin, A T‐cell derived cytokine, upregulates stromelysin‐1 gene expression in human dermal fibroblasts: Evidence for the role of AP‐1 in transcriptional activiation
Author(s) -
Mauviel Alain,
Kähäri VeliMatti,
Uitto Jouni,
Kurkinen Markku,
Evans Charles H.
Publication year - 1992
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.240500110
Subject(s) - cytokine , microbiology and biotechnology , gene expression , chemistry , gene , cell , biology , immunology , biochemistry
Leukoregulin(LR), a product of activated T‐cells, has been recently shown to modulate the metabolism of extracellular matrix components in human skin fibroblast cultures (Mauviel et al., J Cell Biol 113:1455–1462, 1991). In this study we focused our attention on the effects of LR on the expression of stromelysin‐1 gene. This matrix metalloprotease has a broad spectrum of degradative activity and it is also required for maximal activation of interstitial collagenase. Incubation of skin fibroblast cultures with LR resulted in a dose‐ and time‐dependent elevation of stromelysin‐1 mRNA levels, the maximum enhnacement being up to approximately sevenfold. This effect was abolished by cycloheximide, suggesting a requirement for ongoing protein synthesis. Transient cell transfections with a promoter/ reporter gene construct containing 1.3 kb of 5′ flanking DNA of the human stromelysin‐1 gene linked to the chloramphenicol acetyl transferase (CAT) gene, indicated enhancement of promoter activity by LR. This inhancement was abolished by a single base substitution in the AP‐1 binding site of the promoter. Furthermore, gel mobility shift assays demonstrated enhanced AP‐1 binding activity in nuclear extracts from cells incubated with LR. However, LR did not alter the activity of a construct containing three AP‐1 sequences in front of the thymidine kinase promoter linked to the CAT gene. These results collectively suggest that activation of stromelysin‐1 gene expression by LR is mediated by AP‐1 regulatory elements which are necessary, but not sufficient, for gene response. © 1992 Wiley‐Liss, Inc.