Ganter S, Northoff H, Männel D, Gebicke-Härter P J
Institute of Pharmacology, University of Freiburg, Germany.
J Neurosci Res. 1992 Oct;33(2):218-30. doi: 10.1002/jnr.490330205.
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.
小胶质细胞是脑内的常驻巨噬细胞，通常对损伤或慢性疾病会产生增殖反应并表达分化特征，如产生与炎症事件相关的细胞因子。因此，小胶质细胞因子表达的调控是科学研究的一个主要关注点。研究表明，粒细胞-巨噬细胞集落刺激因子（GMCSF）和白细胞介素-3（Il-3）是小胶质细胞的有效促有丝分裂原。此外，Il-3和其他细胞因子是小胶质细胞的产物。本文表明，白细胞介素-1（Il-1）以及肿瘤坏死因子（TNFα）可增加星形胶质细胞-小胶质细胞混合培养物中小胶质细胞的增殖，但对分离的小胶质细胞没有促有丝分裂作用。细菌内毒素脂多糖（LPS）在星形胶质细胞-小胶质细胞混合培养物和分离的小胶质细胞培养物中均不可逆地抑制小胶质细胞的分裂。相比之下，皮质类固醇氢化可的松和醛固酮以及合成糖皮质激素地塞米松可可逆地抑制小胶质细胞的增殖。它们还拮抗Il-3和粒细胞巨噬细胞集落刺激因子（GMCSF）的刺激作用。雌二醇和孕酮对混合培养物没有显著影响，但在分离培养物中抑制小胶质细胞的增殖。来自混合培养物、分离培养物、WEHI-2B细胞系或新鲜（补充血清）培养基的条件培养基在不同程度上刺激小胶质细胞的增殖。总之，细胞因子介导的小胶质细胞增殖可被多种类固醇激素下调。由于皮质类固醇通常能够不受阻碍地作用于脑细胞，它们可能对小胶质细胞的增殖保持抑制作用。据推测，在脑损伤和修复过程中，这种抑制作用会在局部和暂时被克服。
