Induction of metallothionein in astrocytes by cytokines and heavy metals.
Immunohistochemical staining of human and rat brains for metallothionein (MT) using a monoclonal anti-MT antibody (MT45) revealed that protoplasmic astrocytes, which are densely localized in the gray matter, contain high levels of MT. Human U373MG astrocytoma cells were stimulated with interleukin (IL)-1 or heavy metals to produce MT. When expression of MT in U373MG cells was analyzed by Northern blotting or indirect immunofluorescence using the MT45 antibody, it was found that IL-1 (> or = 10 U/ml), CdCl2 (50 microM) and high concentrations of ZnCl2 (500 microM) induced marked biosynthesis of MT.IL-6 (up to 3,000 U/ml) and lower concentrations of ZnCl2 (10-50 microM), however, showed little inducing activity. Hippocampal astrocytes in primary culture produced a relatively high basal level of MT. The MT level increased in response to addition of IL-1 (> or = 10 U/ml), ZnCl2 (50 microM) and CdCl2 (5 microM). However, the increase induced by IL-6 (1,000 U/ml) was not very marked. The in vivo induction of MT in the brain by cytokines is not fully understood. However, our data and other indirect evidence suggest that IL-1 may be a potent stimulator of MT induction in astrocytes. Furthermore, the astrocytoma cell line, U373MG, is a suitable in vitro system to analyze the expression of MT in astrocytes.
Division of Biochemistry and Immunochemistry, National Institute of Health Sciences, Tokyo, Japan.
J
J
Sawada
Y
Y
Kikuchi
M
M
Shibutani
K
K
Mitsumori
K
K
Inoue
T
T
Kasahara
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001921:Brain / Q000502:physiology; D002104:Cadmium / Q000494:pharmacology; D019256:Cadmium Chloride; D002478:Cells, Cultured; D002712:Chlorides / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000494:pharmacology; D008668:Metallothionein / Q000096:biosynthesis* / Q000502:physiology; D051381:Rats; D015398:Signal Transduction; D017967:Zinc Compounds / Q000494:pharmacology
D002712:Chlorides; D007375:Interleukin-1; D017967:Zinc Compounds; D002104:Cadmium; C016837:zinc chloride; D008668:Metallothionein; D019256:Cadmium Chloride