Protein tyrosine kinase inhibitors decrease lipopolysaccharide-induced proinflammatory cytokine production in mixed glia, microglia-enriched or astrocyte-enriched cultures
Protein tyrosine kinase inhibitors decrease lipopolysaccharide-induced proinflammatory cytokine production in mixed glia, microglia-enriched or astrocyte-enriched cultures
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DOI：
10.1016/s0197-0186(96)00086-1
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发表时间：
1997-04-01
影响因子：
4.2
通讯作者：
Hong, JS
中科院分区：
文献类型：
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作者：
Kong, LY;Lai, C;Hong, JS
胶质细胞产生的促炎细胞因子、肿瘤坏死因子- α (TNF α)、白细胞介素-1 （IL-1）和白细胞介素-6 （IL-6）与多种疾病的神经发病机制有关。然而，神经胶质细胞中产生这些细胞因子的信号转导途径尚不清楚。本研究检测了两种有效的蛋白酪氨酸激酶抑制剂染料木黄酮和tyrphostin A25对小鼠原代混合胶质细胞、小胶质细胞或星形胶质细胞富集培养物中脂多糖（LPS）诱导的TNF α、IL-1 α和IL-6产生的影响。LPS剂量依赖性地增加了混合胶质细胞培养中TNF α、IL-1 α和IL-6的产生。染料木素或tyrphostin A25显著抑制lps诱导的这些细胞因子的产生。在小胶质细胞或星形胶质细胞富集的培养物中，lps诱导的TNF α、IL-1 α和IL-6的产生也被tyrphostin A25抑制。这些结果表明，蛋白酪氨酸激酶参与了小胶质细胞或星形胶质细胞中脂多糖诱导的TNF α、IL-1 α或IL-6产生的信号传导事件，这可能为大脑中细胞因子产生途径的治疗干预提供见解。Elsevier Science Ltd.出版。
Proinflammatory cytokines, tumor necrosis factor-alpha (TNF alpha), interleukin-1 (IL-1), and interleukin-6 (IL-6), produced by glial cells have been implicated in the neuropathogenesis of various diseases. However, the signal transduction pathway(s) for the production of these cytokines in glial cells are not well understood. This study examined the effects of two potent protein tyrosine kinase inhibitors, genistein and tyrphostin A25, on lipopolysaccharide (LPS)-induced production of TNF alpha, IL-1 alpha, and IL-6 in mouse primary mixed glia, microglia- or astrocyte-enriched cultures. LPS dose-dependently increased the production of TNF alpha, IL-1 alpha, and IL-6 from the mixed glia cultures. Genistein or tyrphostin A25 significantly inhibited the LPS-induced production of these cytokines. The LPS-induced TNF alpha, IL-1 alpha, and IL-6 production in microglia- or astrocyte-enriched cultures were also inhibited by tyrphostin A25. These results demonstrate that protein tyrosine kinases are involved in the signaling events of the LPS-induced production of TNF alpha, IL-1 alpha, or IL-6 in microglia or astrocytes, which may provide insights into therapeutic interventions in the pathway for cytokine production in the brain. Published by Elsevier Science Ltd.