CLUSTERIN EXPRESSION BY ASTROCYTES IS INFLUENCED BY TRANSFORMING GROWTH-FACTOR-BETA-1 AND HETEROTYPIC CELL-INTERACTIONS

被引:74
作者
MORGAN, TE [1 ]
LAPING, NJ [1 ]
ROZOVSKY, I [1 ]
ODA, T [1 ]
HOGAN, TH [1 ]
FINCH, CE [1 ]
PASINETTI, GM [1 ]
机构
[1] UNIV SO CALIF,DEPT BIOL SCI,LOS ANGELES,CA 90089
关键词
TRANSFORMING GROWTH FACTOR BETA-1; CLUSTERIN; MESSENGER-RNA TRANSCRIPTION; ASTROCYTES; MICROGLIA;
D O I
10.1016/0165-5728(94)00194-S
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
This study characterizes the effect of transforming growth factor (TGF) beta 1 on clusterin expression in rat brain cells. 24 h after an acute unilateral intracerebroventricular infusion of TGF-beta 1, clusterin mRNA prevalence was increased in astrocytes that contained immunoreactive (IR) glial fibrillary acidic protein (GFAP). TGF-beta 1 selectively induced clusterin mRNA in astrocytes, as no clusterin mRNA was detected in neurons, oligodendrocytes, or microglia. TGF-beta 1 induced a bilateral increase in clusterin mRNA per astrocyte. Astrocyte hypertrophy (GFAP-IR area) was only increased on the ipsilateral side. In pure astrocyte cultures, TGF-beta 1 (200 pM) decreased clusterin mRNA levels and the rate of clusterin RNA transcription. However, in cultures of astrocytes that contained microglia and oligodendrocytes (mixed glia cultures), TGF-beta 1 caused a dose-dependent increase in astrocytic clusterin mRNA levels. The astrocytes that responded to TGF-beta 1 included two GFAP-IR subtypes, type 1 and 2. TGF-beta 1 increased clusterin protein in the conditioned medium from cultured glia, in either monotypic or mixed glial cultures. Thus, TGF-beta 1 and heterotypic cell interactions influence clusterin expression by astrocytes and may be important to the role of clusterin in multiple sclerosis, AIDS, and Alzheimer's disease.
引用
收藏
页码:101 / 110
页数:10
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