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Metallothionein is required for zinc‐induced expression of the macrophage colony stimulating factor gene
Author(s) -
Kanekiyo Masako,
Itoh Norio,
Kawasaki Atsuko,
Matsuda Kimihiro,
Nakanishi Tsuyoshi,
Tanaka Keiichi
Publication year - 2002
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.10202
Subject(s) - cycloheximide , metallothionein , gene expression , microbiology and biotechnology , biology , messenger rna , downregulation and upregulation , regulation of gene expression , gene , chemistry , protein biosynthesis , biochemistry
Macrophage colony stimulating factor (M‐CSF) plays an important role in the proliferation and differentiation of mononuclear phagocytes. The present study investigates the effect of zinc on M‐CSF expression in MC3T3‐E1 and L929 cells. Zinc dose‐dependently increased M‐CSF mRNA levels. The time‐course of zinc‐induced M‐CSF mRNA expression peaked at 6 h. Stability studies of mRNA using actinomycin D revealed that zinc does not affect M‐CSF mRNA stability. We examined the function of the M‐CSF gene promoter using a luciferase reporter assay. A construct containing the −467/+39 region of the promoter was upregulated by zinc. In the presence of cycloheximide, zinc did not induce a greater increase in the M‐CSF mRNA than cycloheximide alone. To confirm the effect of MT on M‐CSF mRNA expression, mouse lung fibroblasts (MLFs) were prepared from MT+/+ and MT−/− mice. Zinc induced an increase in the expression of M‐CSF in MT+/+ MLFs, but this response was not evident in MT−/− MLFs. Moreover, overexpression of MT upregulated M‐CSF mRNA expression as well as M‐CSF secretion. Our findings suggest that MT expression mediates zinc regulation of M‐CSF gene expression at the transcriptional level. J. Cell. Biochem. 86: 145–153, 2002. © 2002 Wiley‐Liss, Inc.