Involvement of proton-sensing receptor TDAG8 in the anti-inflammatory actions of dexamethasone in peritoneal macrophages
Involvement of proton-sensing receptor TDAG8 in the anti-inflammatory actions of dexamethasone in peritoneal macrophages
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DOI：
10.1016/j.bbrc.2011.10.122
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发表时间：
2011-12-02
影响因子：
3.1
通讯作者：
Okajima, Fumikazu
中科院分区：
文献类型：
--
作者：
He, Xiao-dong;Tobo, Masayuki;Okajima, Fumikazu
地塞米松（DEX）是一种有效的糖皮质激素，可增加t细胞死亡相关基因8 （TDAG8）的表达，TDAG8是一种质子感应G蛋白偶联受体，与酸性ph诱导的cAMP积累增强有关。我们探讨了TDAG8表达增加在DEX抗炎作用中的作用。DEX或酸性pH处理巨噬细胞均可诱导巨噬细胞死亡；然而，TDAG8缺乏对细胞死亡没有影响。在中性pH下，DEX抑制脂多糖诱导的肿瘤坏死因子-a（一种独立于TDAG8的炎症细胞因子）的产生，而糖皮质激素则以依赖于TDAG8的方式增强酸性pH诱导的肿瘤坏死因子-a产生的抑制。综上所述，在酸性pH环境下，dex诱导的TDAG8表达增加部分参与了糖皮质激素诱导的抗炎作用，通过抑制炎症细胞因子的产生。另一方面，TDAG8在dex诱导的细胞死亡中的作用尚不明确。(C) 2011爱思唯尔公司版权所有。
Dexamethasone (DEX), a potent glucocorticoid, increased the expression of T-cell death associated gene 8 (TDAG8), a proton-sensing G protein-coupled receptor, which is associated with the enhancement of acidic pH-induced cAMP accumulation, in peritoneal macrophages. We explored the role of increased TDAG8 expression in the anti-inflammatory actions of DEX. The treatment of macrophages with either DEX or acidic pH induced the cell death of macrophages; however, the cell death was not affected by TDAG8 deficiency. While DEX inhibited lipopolysaccharide-induced production of tumor necrosis factor-a, an inflammatory cytokine, which was independent of TDAG8, at neutral pH, the glucocorticoid enhanced the acidic pH-induced inhibition of tumor necrosis factor-a production in a manner dependent on TDAG8. In conclusion, the DEX-induced increase in TDAG8 expression is in part involved in the glucocorticoid-induced anti-inflammatory actions through the inhibition of inflammatory cytokine production under the acidic pH environment. On the other hand, the role of TDAG8 in the DEX-induced cell death is questionable. (C) 2011 Elsevier Inc. All rights reserved.