Gene expression profiling of dexamethasone-treated RBL-2H3 cells: induction of anti-inflammatory molecules
Gene expression profiling of dexamethasone-treated RBL-2H3 cells: induction of anti-inflammatory molecules
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DOI：
10.1016/j.imlet.2004.12.009
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发表时间：
2005-05-15
影响因子：
4.4
通讯作者：
Sawada, J
中科院分区：
文献类型：
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作者：
Nakamura, R;Okunuki, H;Sawada, J
众所周知，糖皮质激素通过调节多种免疫细胞（包括肥大细胞）的基因表达而具有抗炎作用。然而，参与糖皮质激素抑制肥大细胞介导的炎症的基因尚未完全确定。因此，我们使用高密度寡核苷酸微阵列技术检测了RBL-2H3肥大细胞中地塞米松（Dex）应答基因。基因表达谱显示抗原诱导的促炎因子上调，包括单核细胞趋化蛋白-1，被100 nM Dex显著抑制。另一方面，Dex处理本身导致肥大细胞中许多基因的大量上调，包括苯乙醇胺- n -甲基转移酶（PNMT）和细胞因子诱导的含sh2蛋白（CISH）。这两个基因的表达在Dex暴露后6 h显著升高，且持续时间超过24 h。考虑到PNMT是肾上腺素合成的速率决定酶，CISH是细胞因子信号的抑制因子，这些Dex应答基因可能是潜在的抗炎因子。因此，基因表达谱提示右美托咪唑可能通过抑制和诱导潜在的促炎因子和抗炎因子两种途径在肥大细胞中发挥抗炎作用。(c) 2004 Elsevier B.V.版权所有
Glucocorticoids are well known for their anti-inflammatory effect through the regulation of gene expression in many types of immune cells, including mast cells. However, the genes that are involved in suppression of mast cell-mediated inflammation by glucocorticoids have not been fully identified. Therefore, we examined the dexamethasone (Dex) -responsive genes in RBL-2H3 mast cells using a high-density oligonucleotide microarray technique. Gene expression profiling revealed that the antigen-induced up-regulation of pro-inflammatory factors, including monocyte chemoattractant protein-1, was markedly inhibited by 100 nM Dex. On the other hand, Dex treatment itself caused the substantial up-regulation of many genes, including phenylethanolamine-N-methyl transferase (PNMT) and cytokine-inducible SH2-containing protein (CISH), in the mast cells. The expression of these two genes significantly increased 6 h after Dex exposure and lasted for more than 24 h. Considering that PNMT is the rate-determining enzyme in epinephrine synthesis and that CISH is a suppressor of cytokine signaling, these Dex-responsive genes may be potential anti-inflammatory factors. Thus, gene expression profiling suggested that Dex might exert its anti-inflammatory effect through two pathways in mast cells: the suppression and induction of potentially pro- and anti-inflammatory factors, respectively. (c) 2004 Elsevier B.V. All rights reserved.