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

This study characterizes the effect of transforming growth factor (TGF ) beta 1 on clusterin expression in rat brain cells. 24 h after an acu te unilateral intracerebroventricular infusion of TGF-beta 1, clusteri n mRNA prevalence was increased in astrocytes that contained immunorea ctive (IR) glial fibrillary acidic protein (GFAP). TGF-beta 1 selectiv ely induced clusterin mRNA in astrocytes, as no clusterin mRNA was det ected in neurons, oligodendrocytes, or microglia. TGF-beta 1 induced a bilateral increase in clusterin mRNA per astrocyte. Astrocyte hypertr ophy (GFAP-IR area) was only increased on the ipsilateral side. In pur e astrocyte cultures, TGF-beta 1 (200 pM) decreased clusterin mRNA lev els and the rate of clusterin RNA transcription. However, in cultures of astrocytes that contained microglia and oligodendrocytes (mixed gli a cultures), TGF-beta 1 caused a dose-dependent increase in astrocytic clusterin mRNA levels. The astrocytes that responded to TGF-beta 1 in cluded two GFAP-IR subtypes, type 1 and 2. TGF-beta 1 increased cluste rin protein in the conditioned medium from cultured glia, in either mo notypic 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 Al zheimer's disease.