Ganter, S. and Northoff, H. and Männel, Daniela N. and Gebicke-Härter, P. J.
Growth control of cultured microglia.
Journal of neuroscience research 33 (2), pp. 218-230.
Microglia, the resident macrophages of the brain, typically react to injuries or chronic diseases with proliferation and expression of differentiated features, such as production of cytokines associated with inflammatory events. Regulation and control of microglial cytokine expression, therefore, is a major focus of scientific interest. It has been shown that GMCSF and Il-3 are potent mitogens for microglia. Moreover, Il-3 and other cytokines are products of microglia. It is shown here that interleukin-1 (Il-1) as well as tumor necrosis factor (TNF alpha) increased microglial proliferation in mixed astrocyte-microglial cultures but had no mitogenic effects on isolated microglia. Lipopolysaccharide (LPS), the bacterial endotoxin, irreversibly inhibited microglial cell division in both mixed astrocyte-microglial cultures and in isolated microglial cultures. By contrast, the corticosteroids hydrocortisone and aldosterone and the synthetic glucocorticoid dexamethasone reversibly inhibited microglial proliferation. They also antagonized the stimulatory effects of Il-3 and granulocyte macrophage colony-stimulating factor (GMCSF). Estradiol and progesterone had no significant effects on mixed cultures but inhibited microglial proliferation in isolated cultures. Conditioned media from mixed cultures, isolated cultures, from the WEHI-2B cell line, or from fresh (serum-supplemented) media stimulated microglial proliferation to various extents. In summary, cytokine-mediated microglial proliferation can be down-regulated by a variety of steroid hormones. Along with their unimpaired access to brain cells in general, corticosteroids likely maintain an inhibitory tonus on microglial proliferation. It is hypothesized that this inhibition is overcome locally and temporally in brain injury and repair.
|Institutions:|| Medicine > Lehrstuhl für Immunologie|
|Acid Anhydride Hydrolases||MESH|
|Cell Division/drug effects||MESH|
|Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology||MESH|
|Phosphoric Monoester Hydrolases/metabolism||MESH|
|Tumor Necrosis Factor-alpha/biosynthesis||MESH|
|Subjects:||600 Technology > 610 Medical sciences Medicine|
|Refereed:||Yes, this version has been refereed|
|Created at the University of Regensburg:||Unknown|
|Deposited On:||17 Jun 2011 06:09|
|Last Modified:||22 Oct 2012 08:10|