IL-13 down-regulates CD14 expression and TNF-alpha secretion in normal human monocytes.
IL-13 down-regulates CD14 expression and TNF-alpha secretion in normal human monocytes.
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DOI：
10.4049/jimmunol.155.6.3145
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发表时间：
1995-09
影响因子：
4.4
通讯作者：
G. Cosentino;E. Soprana;C. Thienes;A. Siccardi;G. Viale;D. Vercelli
中科院分区：
文献类型：
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作者：
G. Cosentino;E. Soprana;C. Thienes;A. Siccardi;G. Viale;D. Vercelli
CD 14是一种糖基磷脂酰肌醇（GPI）连接蛋白，在单核细胞和中性粒细胞上表达，调节单核细胞-淋巴细胞相互作用，并作为LPS受体。我们先前表明，IL-4通过在转录水平上起作用下调人CD 14的表达。我们现在研究是否CD 14的表达也可以调节IL-13，5号染色体细胞因子基因家族的另一个成员。IL-13剂量依赖性地抑制人单核细胞上的CD 14表达。与此相反，CD 23和CD 11b的表达强烈增强。CD 14的下调既不涉及脱落，也不涉及内源性GPI锚裂解酶的激活。事实上，可溶性CD 14在IL-13刺激的单核细胞的上清液中没有增加，并且另一种GPI连接的蛋白质CD 55/CD 14的表达不受IL-13的影响。在IL-13处理的单核细胞中，CD 14转录物水平降低了6倍。这些结果表明，IL-13通过抑制CD 14 RNA表达下调膜CD 14。IL-13依赖性下调CD 14导致CD 14介导的事件的抑制。事实上，在与IL-13预孵育72小时后，用LPS（100 ng/ml）刺激的单核细胞中，CD 14介导的TNF-α释放被显著抑制（约75%）。然而，IL-13也直接抑制单核因子分泌，因为它阻断PMA诱导的、CD 14非依赖性TNF-α释放。CD 14和TNF-α分泌的下调可能在IL-13对LPS刺激的单核细胞的抗炎作用中发挥重要作用。
CD14, a glycosylphosphatidylinositol (GPI)-linked protein expressed on monocytes and neutrophils, regulates monocyte-lymphocyte interactions and serves as the LPS receptor. We showed previously that IL-4 down-regulates the expression of human CD14 by acting at the transcriptional level. We now investigate whether CD14 expression could also be regulated by IL-13, another member of the chromosome 5 cytokine gene family. IL-13 dose-dependently inhibited CD14 expression on human monocytes. By contrast, expression of CD23 and CD11b was enhanced strongly. Down-regulation of CD14 involved neither shedding nor activation of endogenous GPI anchor-cleaving enzymes. Indeed, soluble CD14 was not increased in the supernatants of IL-13-stimulated monocytes, and expression of CD55/DAF, another GPI-linked protein, was unaffected by IL-13. CD14 transcript levels were reduced sixfold in IL-13-treated monocytes. These results suggest that IL-13 down-regulates membrane CD14 by suppressing CD14 RNA expression. IL-13-dependent down-regulation of CD14 resulted in the inhibition of CD14-mediated events. Indeed, CD14-mediated release of TNF-alpha was inhibited markedly (approximately 75%) in monocytes stimulated with LPS (100 ng/ml) after a 72-h preincubation with IL-13. However, IL-13 also directly inhibited monokine secretion, because it blocked PMA-induced, CD14-independent TNF-alpha release. Down-regulation of CD14 and TNF-alpha secretion may play a major role in the anti-inflammatory effects of IL-13 on LPS-stimulated monocytes.