Effects of Transforming Growth Factor β1 on Astroglial Cells in Culture

Abstract

The effects of transforming growth factor beta 1 (TGF beta 1) on DNA synthesis and functional differentiation of astroglial cells cultured in serum-free medium were investigated. TGF beta 1 diminished and delayed the peak of DNA synthesis induced by serum. TGF beta 1-treated cells were larger than control cells. This factor delayed the appearance of process-bearing cells induced by acidic fibroblast growth factor treatment and also affected the astrocyte-specific enzyme glutamine synthetase (GS), whose accumulation is under hydrocortisone (HC) control. TGF beta 1 inhibited the induction of GS activity by HC in a dose- and time-dependent manner. Moreover, pretreatment with TGF beta 1 for 4 h maintained the inhibition of GS activity for approximately 16 h after removal of this factor from culture medium. These results suggest that TGF beta 1 may be an important regulator of astrocyte growth and differentiation.

Effects of transforming growth factor-beta on murine astrocyte glutamine synthetase activity. Implications in neuronal injury.

“…Astrocyte GS activity is inhibited by TGF-f3 exposure when cells are stimulated with hydrocortisone (43). Since GS is found exclusively in astrocytes ( 18,19), inhibition ofGS activity may in turn increase the vulnerability ofcultured neurons to glutamate neurotoxicity.…”

Macrophages and HIV-1: dangerous liaisons

“…This strongly suggests a compensatory mechanism that responds to depressed astrocytic function. Indeed, substances released by infected AMM, such as gp120 (Vesce et al, 1997) TNF- (Fine et al, 1996, PAF (Nishida et al, 1996) and TGF-ß (Chao et al, 1992;Toru-Delbauffe et al, 1990), inhibit glutamate uptake by astrocytes and glutamine synthetase activity and induce glutamate release (Bezzi et al, 2001). Conversely, TNF- induces EAAT function in differentiating monocytes (Rimaniol et al, 2000).…”

Transforming growth factor-beta 1 reduces infarct size after experimental cerebral ischemia in a rabbit model.

“…15 Of interest, TGF-/31 has recently been shown to suppress some aspects of astrocyte function in vitro. 16 The ability of TGF-/31 to afford cardioprotection in a model of myocardial ischemia 17 as well as its demonstrated suppression of both leukocyte 13 - 14 and astrocyte 16 function suggests a potential beneficial role for this peptide in acute cerebral ischemia. In the present study, we examined the effect of the most abundant isoform, TGF-/31, in a rabbit model of thromboembolic stroke.…”

“…16 Astrocytes are capable of producing various cytokines such as tumor necrosis factor (TNF). 26 Interestingly, both an exaggerated release and deleterious effect of TNF have been demonstrated in a model of cardiac ischemia.…”