PPARalpha ligands inhibit radiation-induced microglial inflammatory responses by negatively regulating NF-kappaB and AP-1 pathways.
PPARalpha ligands inhibit radiation-induced microglial inflammatory responses by negatively regulating NF-kappaB and AP-1 pathways.
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DOI：
10.1016/j.freeradbiomed.2008.09.002
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发表时间：
2008-12-15
影响因子：
7.4
通讯作者：
Robbins ME
中科院分区：
文献类型：
--
作者：
Ramanan S;Kooshki M;Zhao W;Hsu FC;Robbins ME
全脑照射（WBI）可导致照射后数月至数年的认知障碍。对啮齿类动物的研究表明，脑照射后激活的小胶质细胞（脑巨噬细胞）迅速持续增加，导致慢性炎症反应和海马神经发生相应减少。因此，减轻辐射后的小胶质细胞活化是减少WBI诱导的发病率的关键策略。我们假设用过氧化物酶体增殖物激活受体（PPAR）α激动剂预处理将改善体外辐射后小胶质细胞中观察到的促炎反应。用单剂量（2-10戈伊）的137 Cs γ射线照射BV-2细胞（一种小鼠小胶质细胞系）导致1] IL-1β和TNFα基因表达增加，2]考克斯-2蛋白水平增加和3]细胞内ROS产生增加。此外，观察到氧化还原调节的促炎性转录因子AP-1和NF-κB的DNA结合活性增加。用PPARα激动剂GW 7647和非诺贝特预处理BV-2细胞显著抑制辐射诱导的小胶质细胞促炎反应，部分是通过减少i] NF-κB p65亚基的核转位和ii]细胞核中AP-1的c-jun亚基的磷酸化。综上所述，这些数据支持以下假设：PPARα的激活可以调节辐射诱导的小胶质细胞促炎反应。
Whole-brain irradiation (WBI) can lead to cognitive impairment several months to years after irradiation. Studies on rodents have shown a rapid and sustained increase in activated microglia (brain macrophages) following brain irradiation, contributing to a chronic inflammatory response and a corresponding decrease in hippocampal neurogenesis. Thus, alleviating microglial activation following radiation represents a key strategy to minimize WBI-induced morbidity. We hypothesized that pre-treatment with peroxisomal proliferator-activated receptor (PPAR)α agonists would ameliorate the pro-inflammatory responses seen in the microglia following in vitro radiation. Irradiating BV-2 cells (a murine microglial cell line) with single doses (2-10 Gy) of 137Cs γ-rays led to increases in 1] the gene expression of IL-1β and TNFα, 2] Cox-2 protein levels and 3] intracellular ROS generation. In addition, an increase in the DNA-binding activity of redox-regulated pro-inflammatory transcription factors AP-1 and NF-κB was observed. Pre-treating BV-2 cells with the PPARα agonists, GW7647 and Fenofibrate significantly inhibited the radiation-induced microglial pro-inflammatory response, in part, via decreasing i] the nuclear translocation of the NF-κB p65 subunit and ii] phosphorylation of the c-jun subunit of AP-1 in the nucleus. Taken together, these data support the hypothesis that activation of PPARα can modulate the radiation-induced microglial pro-inflammatory response.
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影响因子：
6.1
作者：
Hwang, SY;Jung, JS;Han, IO
通讯作者：
Han, IO
影响因子：
4.4
作者：
Jana, Malabendu;Jana, Arundhati;Pahan, Kalipada
通讯作者：
Pahan, Kalipada
影响因子：
3.3
作者：
BLASI, E;BARLUZZI, R;BISTONI, F
通讯作者：
BISTONI, F
影响因子：
5.3
作者：
Choi, SH;Lee, DY;Jin, BK
通讯作者：
Jin, BK
DOI：
10.1016/0360-3016(95)00279-8
发表时间：
1995-10-15
影响因子：
7
作者：
HONG, JH;CHIANG, CS;MCBRIDE, WH
通讯作者：
MCBRIDE, WH