Anti-inflammatory roles of retinoic acid in rat brain astrocytes:: Suppression of interferon-γ-induced JAK/STAT phosphorylation
Anti-inflammatory roles of retinoic acid in rat brain astrocytes:: Suppression of interferon-γ-induced JAK/STAT phosphorylation
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DOI：
10.1016/j.bbrc.2005.01.110
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发表时间：
2005-04-01
影响因子：
3.1
通讯作者：
Joe, EH
中科院分区：
文献类型：
--
作者：
Choi, WH;Ji, KA;Joe, EH
维甲酸（RA）的抗炎作用已经研究了几十年。然而，这种影响的潜在机制在很大程度上是未知的。在这项研究中，我们证明，9-顺式RA（cRA）和全反式RA（tRA）抑制干扰素-γ（IFN-γ）诱导的星形胶质细胞的炎症反应。在原代培养的大鼠脑星形胶质细胞和C6星形胶质细胞瘤细胞中，cRA和tRA均降低IFN-γ诱导的干扰素调节因子-1的表达。两种RA同种型也减少IFN-γ诱导的信号转导和转录激活因子（STAT）1、STAT 3、Janus激酶（JAK）1和JAK 2的激活。当在IFN-γ之前用RA预处理细胞时，这种抑制作用是显著的。此外，在放线菌酮的存在下，预处理的RA的效果被取消，表明从头蛋白质合成的要求。细胞因子信号转导抑制因子（SOCS）是JAK/STAT通路的负性调节因子，可能是RA抗炎作用的候选介质。cRA和tRA均诱导SOCS 3 mRNA表达。这些结果表明，RA通过抑制IFN-γ处理的星形胶质细胞中JAK/STAT通路的激活来诱导抗炎作用。SOCS 3可能是介导RA抗炎作用的机制之一。(C)2005年爱思唯尔公司All rights reserved.
The anti-inflammatory effect of retinoic acid (RA) has been investigated for several decades. However, the underlying mechanisms responsible for this effect are largely unknown. In this study, we demonstrate that 9-cis-RA (cRA) and all-trans-RA (tRA) inhibit interferon-gamma (IFN-gamma)-induced inflammatory responses in astrocytes. In primary cultured rat brain astrocytes and C6 astroglioma cells, both cRA and tRA decreased IFN-gamma-induced expression of interferon regulatory factor-1. Both RA isoforms also reduced IFN-gamma-induced activation of signal transducers and activators of transcription (STAT)1, STAT3, Janus kinase (JAK)1, and JAK2. This inhibitory effect was significant when cells were pre-treated with RA prior to IFN-gamma. Furthermore, the effect of pre-treated RA was abolished in the presence of cycloheximide, indicating a requirement for de novo protein synthesis. Suppressors of cytokine signaling (SOCS), which are negative regulators of the JAK/STAT pathway, may be candidate mediators of the anti-inflammatory function of RA. Both cRA and tRA induced SOCS3 mRNA expression. These results suggest that RA induces an anti-inflammatory effect by suppressing the activation of the JAK/STAT pathway in IFN-gamma-treated astrocytes. SOCS3 may be at least one of the mechanisms that mediate the anti-inflammatory roles of RA. (C) 2005 Elsevier Inc. All rights reserved.