Lactate induces tumour necrosis factor-α, interleukin-6 and interleukin-1β release in microglial- and astroglial-enriched primary cultures
Lactate induces tumour necrosis factor-α, interleukin-6 and interleukin-1β release in microglial- and astroglial-enriched primary cultures
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DOI：
10.1111/j.1471-4159.2005.03132.x
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发表时间：
2005-06-01
影响因子：
4.7
通讯作者：
Hansson, E
中科院分区：
文献类型：
--
作者：
Andersson, AK;Rönnbäck, L;Hansson, E
高氨血症对肝功能障碍患者的CNS有有害影响。高氨血症影响的细胞机制在很大程度上是未知的，尽管星形胶质细胞是主要的目标。本研究调查了如何与NH 4Cl和乳酸，这增加了在大脑中作为高氨血症的结果，影响细胞在原代大鼠培养物中富含星形胶质细胞或小胶质细胞的治疗。使用光学显微镜研究随时间的形态学变化。使用ELISA测量促炎细胞因子肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-6和IL-1 β的释放。NH_4Cl在两种培养体系中都能诱导液泡形成。乳酸盐处理改变了星形胶质细胞的外观，导致单个细胞之间的空间增加。NH 4Cl或乳酸处理的小胶质细胞均呈圆形。乳酸盐，而不是NH 4Cl，诱导释放的TNF-α和IL-6在星形胶质细胞和小胶质细胞丰富的文化，而IL-1 β仅在小胶质细胞的文化。细胞因子的释放在小胶质细胞中高于星形胶质细胞富集培养物。此外，含有约10%小胶质细胞的星形胶质细胞富集培养物比含有约5%小胶质细胞的培养物释放更多的细胞因子。总之，我们的数据表明，大多数TNF-α，IL-6和IL-1 β的释放来自小胶质细胞。因此，小胶质细胞可能在高氨血症的病理过程中发挥重要作用。
Hyperammonaemia has deleterious effects on the CNS in patients with liver dysfunction. Cellular mechanisms underlying the effects of hyperammonaemia are largely unknown, although astrocytes have been the main target of interest. This study investigated how treatment with NH4Cl and lactate, which increase in the brain as a consequence of hyperammonaemia, affects cells in primary rat cultures enriched in either astrocytes or microglia. Morphological changes were studied over time using light microscopy. Release of the proinflammatory cytokines tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-6 and IL-1 beta was measured using ELISA. NH4Cl was found to induce vacuole formation in both culture systems. Lactate treatment altered astrocytic appearance, resulting in increased space between individual cells. Microglia adopted a round morphology with either NH4Cl or lactate treatment. Lactate, but not NH4Cl, induced release of TNF-alpha and IL-6 in both astroglial- and microglial-enriched cultures, while IL-1 beta was released only in microglial cultures. Cytokine release was higher in the microglial- than in the astroglial-enriched cultures. Additionally, the astroglial-enriched cultures containing approximately 10% microglial cells released more cytokines than cultures containing about 5% microglial cells. Taken together, our data suggest that most TNF-alpha, IL-6 and IL-1 beta release comes from microglia. Thus, microglia could play an important role in the pathological process of hyperammonaemia.