Osmotic regulation of cytokine synthesis in vitro
Osmotic regulation of cytokine synthesis in vitro
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DOI：
10.1073/pnas.92.26.12230
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发表时间：
1995-12-19
影响因子：
11.1
通讯作者：
Dinarello, CA
中科院分区：
文献类型：
--
作者：
Shapiro, L;Dinarello, CA
这些研究旨在探讨KI饱和溶液用于治疗感染性和炎症性疾病的治疗机制。在体外培养的人外周血单核细胞中加入12-50 mM KI，可产生319-395 mM的最终溶质浓度，并可诱导IL-8的合成。当加入40 mM盐(375molM)时，IL-8产生最大，与IL-1α内毒素诱导产生的IL-8相当。然而，没有诱导IL-1α、IL-1β或肿瘤坏死因子来解释IL-8的合成；KI的作用不是由于污染了内毒素。高渗氯化钠也可诱导IL-8，并使IL-8mRNA的稳态水平升高，与IL-1α诱导的水平相似。外周血单核细胞经高渗氯化钠孵育96h后，IL-8基因表达水平升高。在人THP-1巨噬细胞中，KI、NaI或NaC l的渗透刺激也可诱导IL-8的产生。IL-1信号转导包括渗透胁迫后观察到的p38丝裂原活化蛋白激酶的磷酸化。通过对该激酶的特异性阻断，高渗氯化钠诱导的IL-1可被剂量效应抑制。因此，这些研究表明，IL-1和渗透性休克利用相同的丝裂原活化蛋白激酶进行信号转导和IL-8合成。
These studies were undertaken to investigate the therapeutic mechanism of saturated solution of KI, used to treat infectious and inflammatory diseases. The addition of 12-50 mM KI to cultured human peripheral blood mononuclear cells resulted in 319-395 mosM final solute concentration and induced interleukin (IL)-8 synthesis. Maximal IL-8 production was seen when 40 mM salt was added (375 mosM) and was equal to IL-8 induced by endotoxin of IL-1 alpha. However, there was no induction of IL-1 alpha, IL-1 beta, or tumor necrosis factor to account for the synthesis of IL-8; the effect of KI was not due to contaminating endotoxins. Hyperosmolar NaCl also induced IL-8 and increased steady-state levels of IL-8 mRNA similar to those induced by IL-1 alpha. IL-8 gene expression was elevated for 96 hr in peripheral blood mononuclear cells incubated with hyperosmolar NaCl. In human THP-1 macrophagic cells, osmotic stimulation with KI, NaI, or NaCl also induced IL-8 production. IL-1 signal transduction includes the phosphorylation of the p38 mitogen-activated protein kinase that is observed following osmotic stress. Using specific blockade of this kinase, a dose-response inhibition of hyperosmolar NaCl-induced IL-1. Thus, these studies suggest that IL-1 and osmotic shock utilize the same mitogen-activated protein kinase for signal transduction and IL-8 synthesis.