Effects of dexamethasone on Muc5ac mucin production by primary airway goblet cells
Effects of dexamethasone on Muc5ac mucin production by primary airway goblet cells
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DOI：
10.1152/ajplung.00104.2004
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发表时间：
2005-01-01
影响因子：
4.9
通讯作者：
Kim, KC
中科院分区：
文献类型：
--
作者：
Lu, WJ;Lillehoj, EP;Kim, KC
与气道炎症相关的粘液分泌过多可通过糖皮质激素减少。糖皮质激素介导的抑制粘液产生的机制有两种，一种是通过气道上皮细胞直接抑制粘液产生，另一种是通过间接抑制刺激粘液产生的促炎介质。在本研究中，我们检测了地塞米松（DEX）对A549人肺腺癌细胞MUC5AC mRNA表达和合成的影响，以及对原代大鼠气管表面上皮（RTSE）细胞MUC5AC和总高分子量（HMW）粘蛋白的影响。结果表明，在原代RTSE细胞中，DEX 1)剂量依赖性地抑制Muc5ac mRNA水平，但细胞Muc5ac蛋白和HMW粘蛋白水平未受影响；2)不影响组成型或utp刺激的粘蛋白分泌；3)加强Muc5ac的翻译；4)通过抑制蛋白酶体降解以外的机制增加了细胞内Muc5ac蛋白的稳定性。然而，在A549细胞中，DEX以剂量依赖的方式抑制MUC5AC mRNA水平和MUC5AC蛋白分泌。我们得出结论，尽管DEX抑制原代RTSE细胞中Muc5ac mRNA的水平，但由于翻译和蛋白质稳定性的增加，Muc5ac蛋白的水平保持不变。有趣的是，DEX的一些作用在细胞系中是相反的。
Mucus hypersecretion associated with airway inflammation is reduced by glucocorticoids. Two mechanisms of glucocorticoid-mediated inhibition of mucus production have been proposed, direct inhibition of mucus production by airway epithelial cells and indirectly through inhibition of proinflammatory mediators that stimulate mucus production. In this study, we examined the effect of dexamethasone (DEX) on mRNA expression and synthesis of MUC5AC by A549 human lung adenocarcinoma cells as well as Muc5ac and total high-molecular-weight (HMW) mucins by primary rat tracheal surface epithelial (RTSE) cells. Our results showed that in primary RTSE cells, DEX 1) dose dependently suppressed Muc5ac mRNA levels, but the levels of cellular Muc5ac protein and HMW mucins were unaffected; 2) did not affect constitutive or UTP-stimulated mucin secretion; 3) enhanced the translation of Muc5ac; and 4) increased the stability of intracellular Muc5ac protein by a mechanism other than the inhibition of the proteasomal degradation. In A549 cells, however, DEX suppressed both MUC5AC mRNA levels and MUC5AC protein secretion in a dose-dependent manner. We conclude that whereas DEX inhibits the levels of Muc5ac mRNA in primary RTSE cells, the levels of Muc5ac protein remain unchanged as a consequence of increases in both translation and protein stability. Interestingly, some of the effects of DEX were opposite in a cell line.