Modulation of P2X7 nucleotide receptor expression by pro- and anti-inflammatory stimuli in THP-1 monocytes
Modulation of P2X7 nucleotide receptor expression by pro- and anti-inflammatory stimuli in THP-1 monocytes
复制标题
DOI：
10.1002/jlb.64.2.265
复制
发表时间：
1998-08-01
影响因子：
5.5
通讯作者：
Dubyak, GR
中科院分区：
文献类型：
--
作者：
Humphreys, BD;Dubyak, GR
P2 X（7）受体表达的调节是令人感兴趣的，因为细胞外ATP对该受体的激活触发单核细胞和巨噬细胞中促炎细胞因子白细胞介素-1 β（IL-1 β）的成熟和释放。我们报道了干扰素-γ（IFN-γ）和肿瘤坏死因子-α（TNF-α）协同诱导人THP-1单核细胞系中P2 X（7）R nRNA和功能反应。诱导是剂量依赖性的，最大功能活性需要1000单位/ml IFN-γ和10 ng/mL TNF-α，孵育36-72 h。脂多糖（LPS）/IFN-γ和TNF-α/IFN-γ对P2 X（7）R功能的上调作用可通过与前列腺素E（2）或细胞渗透性环腺苷酸类似物二丁酰环腺苷酸（Bt（2）cAMP）共孵育而显著减弱。在稳定转染人P2 X（7）cDNA的HEK-293细胞中，Bt（2）cAMP没有显著改变P2 X（7）功能，表明Bt（2）cAMP对P2 X（7）R合成或下游信号转导没有普遍影响。这些研究表明，升高的cAMP负调节P2 X（7）R的表达。
Regulation of P2X(7) receptor expression is of interest because activation of this receptor by extracellular ATP triggers maturation and release of the pro-inflammatory cytokine interleukin-1 beta (IL-1 beta) in monocytes and macrophages. We report that interferon-gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-a) synergistically induce P2X(7)R nRNA and functional responses in the human THP-1 monocytic cell line. Induction was dose dependent, with maximal functional activity requiring 1000 units/ml IFN-gamma and 10 ng/mL TNF-alpha and incubations of 36-72 h. The up-regulation of P2X(7)R function by lipopolysaccharide (LPS)/IFN-gamma and TNF-alpha/IFN-gamma was markedly attenuated by coincubation with prostaglandin E(2)or the cell permeant cyclic AMP analog dibutyryl cAMP (Bt(2)cAMP). Bt(2)cAMP did not significantly alter P2X(7) function in HEK-293 cells stably transfected with the human P2X(7) cDNA, indicating that Bt(2)cAMP does not exert a generalized effect on P2X(7)R synthesis or downstream signal transduction. These studies demonstrate that elevated cAMP negatively modulates P2X(7)R expression.