Differential regulation of interleukin-12 (IL-12), tumor necrosis factor alpha, and IL-1 beta production in human myeloid leukemia cell lines and peripheral blood mononuclear cells.
Differential regulation of interleukin-12 (IL-12), tumor necrosis factor alpha, and IL-1 beta production in human myeloid leukemia cell lines and peripheral blood mononuclear cells.
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DOI：
10.1182/blood.v83.7.1847.bloodjournal8371847
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发表时间：
1994-04
期刊：
影响因子：
20.3
通讯作者：
M. Kubin;JM Chow;G. Trinchieri
中科院分区：
文献类型：
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作者：
M. Kubin;JM Chow;G. Trinchieri
自然杀伤细胞刺激因子或白介素12(NKSF/IL-12)最初是从EB病毒(EBV)转化的B细胞条件培养液中分离纯化出来的。佛波酯对B细胞系产生NKSF/IL-12有很强的刺激作用。虽然单核细胞是外周血中产生NKSF/IL-12的主要细胞，但在脂多糖(LPS)或金黄色葡萄球菌的刺激下，几种髓系白血病细胞系无论是结构性的还是在佛波酯刺激下都不能产生可检测到的NKSF/IL-12。然而，3个细胞系ML-3、HL-60和THP-1对内毒素有显著的反应，并产生显著的NKSF/IL-12，而S只对THP-1细胞有效。当这些细胞系与已知的诱导它们分化的化合物预先孵育时，肿瘤坏死因子α(TNFα)和IL-1β的产生在大多数情况下在具有分化特征的细胞中最大，而在所有三种产生细胞系中，响应内毒素的NKSF/IL-12的产生仅通过二甲基亚砜(DMSO)预培养24小时或通过与干扰素-γ(IFN-γ)的共刺激显著增强。DMSO促进NKSF/IL-12产生的效率在培养2~5天后下降，当细胞获得分化特征时。与二甲基亚砜不同，干扰素-γ可促进NKSF/IL-12的产生，而IL-10和地塞米松则抑制内毒素或S金黄色葡萄球菌刺激的外周血单核细胞中NKSF/IL-12的产生。细胞系对这些可能具有生理相关功能的介质的反应能力为研究它们的作用机制提供了一个组织培养模型。
Natural killer cell-stimulatory factor or interleukin-12 (NKSF/IL-12) was originally identified and purified from the conditioned medium of Epstein-Barr virus (EBV)-transformed B-cell lines. Phorbol diesters were observed to be potent stimulators of NKSF/IL-12 production from the B-cell lines. Although monocytes were found to be the major producers of NKSF/IL-12 in peripheral blood (PB) in response to lipopolysaccharide (LPS) or to Staphylococcus aureus, several myeloid leukemia cell lines tested did not produce detectable NKSF/IL-12 either constitutively or upon stimulation with phorbol diesters. However, three lines, ML-3, HL-60, and THP-1, responded to LPS with significant levels of NKSF/IL-12 production, whereas S aureus was effective only on THP-1 cells. When the cell lines were preincubated with compounds known to induce them to differentiate, production of tumor necrosis factor alpha (TNF alpha) and IL-1 beta was in most cases maximal in cells with differentiated characteristics, whereas NKSF/IL-12 production in response to LPS in all three producing cell lines was significantly enhanced only by pretreatment with dimethylsulfoxide (DMSO) for 24 hours, or by costimulation with interferon gamma (IFN gamma). The efficiency of DMSO enhancement of NKSF/IL-12 production decreased after 2 to 5 days of incubation, when the cells acquired differentiated characteristics. Unlike DMSO, IFN gamma enhanced NKSF/IL-12 production, and IL-10 and dexamethasone inhibited it in cell lines and PB mononuclear cells stimulated by either LPS or S aureus. The ability of the cell lines to respond to these mediators of possibly physiologically relevant function provides a tissue-culture model for studying their mechanism of action.