Gamma-interferon promotes proliferation of adult human astrocytes in vitro and reactive gliosis in the adult mouse brain in vivo.

Abstract

Reactive gliosis is a characteristic response of astrocytes to inflammation and trauma of the central nervous system. To investigate whether soluble factors (cytokines) from inflammatory mononuclear cells that accumulate at lesion sites can provide the cellular signals to initiate gliosis and to identify such cytokines, we have tested and found that supernatants derived from subsets of activated human T lymphocytes (CD8' or CD41) are potent mitogens for cultured human adult astrocytes. This effect is blocked by a neutralizing antibody to -interferon (IFN). Recombinant A consideration in relating relevance of in vitro proliferation results to reactive gliosis in vivo is that gliotic scars seldom develop after insults to the embryonic brain (22-24) but are common features in adult brain injuries. Thus, it becomes important to assess proliferation of astrocytes derived from adult animals, rather than from neonatal ones. We have adopted such a strategy by using adult human astrocytes isolated from surgical brain biopsies and have addressed the following questions. Do activated human T lymphocytes produce sufficient cytokines to induce proliferation of cultured adult human astrocytes; if so, which cytokine (s) (see Results), were treated with trysin and seeded on poly(L-lysine)-coated (10 jag/ml) 9-mm Aclar fluorocarbon coverslips at 10,000 cells per coverslip. These mixed cells were used for the present study; methods for eliminating microglia from rodent glia cultures (leucine methyl ester and silica ingestion) (28-30) were not effective for human preparations. Culture medium was Eagle's minimum essential medium supplemented with 5% (vol/vol) fetal calf serum, Gentamicin (20 gg/ml), and dextrose (1 mg/ml) (all from GIBCO).

CD36 is Involved in Astrocyte Activation and Astroglial Scar Formation

“…The literature suggests several links by which CD36 may regulate these pathways. Proinflammatory factors, such as IL-1, IL-6, MCP-1, and IFN-g, which have been shown to be involved in GFAP expression and astrogliosis (Giulian et al, 1988;Hughes et al, 2002;Okada et al, 2004;Levison et al, 2000;Yong et al, 1991), are elevated in the postischemic brain. In the absence of CD36, the strokeinduced upregulation of these pro-inflammatory molecules is substantially reduced (Kim et al, 2008).…”

“…Literature suggests that inflammation is an essential component for the formation of glial scar. Several inflammatory factors including TGF-b (transforming growth factor b), IFN-g (interferon-g), interleukins (ILs), fibroblast growth factor 2, monocyte chemoattractant protein 1 (MCP-1) as well as blood components are involved in the processes of astrogliosis (Fitch and Silver, 1997;Giulian et al, 1988;Hughes et al, 2002;Levison et al, 2000;Mocchetti et al, 1996;Schachtrup et al, 2010;Yong et al, 1991).…”

Differential effects of cysteamine on heat shock protein induction and cytoplasmic granulation in astrocytes and glioma cells

“…These astrocytes also show an increase in glycogen content, Golgi-membranes, ER, various enzymes activities and numbers of mitochondria. The astrocytes also elaborate more extensive processes und significantly increase their content of GFAP (Miyake et al, 1988;Yong et al, 1991). Reactive gliosis results in the formation of a gliotic scar at the site of injury.…”

Interferon-γ Axis in Graft Arteriosclerosis

“…[95][96][97][98][99][100] However, there have been occasional reports that IFN-␥ can promote VSMC growth by potentiating growth factor signaling under certain in vitro conditions, such as serum deprivation. 40,[101][102][103][104] Similarly, IFN-␥ occasionally results in the proliferation of other mesenchymal cell types [105][106][107][108] and even ECs. 109 We believe that the in vivo setting represents the gold standard to assess whether IFN-␥ has pro-or antiproliferative effects on vascular cells.…”