Toll-like receptor 2 is required for opioids-induced neuronal apoptosis.
Toll-like receptor 2 is required for opioids-induced neuronal apoptosis.
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DOI：
10.1016/j.bbrc.2009.11.074
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发表时间：
2010-01-01
影响因子：
3.1
通讯作者：
Yin, Deling
中科院分区：
文献类型：
--
作者：
Li, Yi;Li, Hui;Zhang, Yi;Sun, Xiuli;Hanley, Gregory A.;LeSage, Gene;Zhang, Ying;Sun, Shenggang;Peng, Ying;Yin, Deling
Toll样受体2（TLR 2）是TLR家族中的关键免疫受体，广泛表达于包括免疫和神经系统在内的各种系统中，并且在控制先天性和适应性免疫应答中起关键作用。我们以前报道过阿片类药物抑制细胞生长并引发细胞凋亡。然而，TLR 2介导阿片类药物引起的细胞凋亡的潜在机制尚不清楚。在这里，我们表明，在初级神经元慢性吗啡治疗显着增加TLR 2的表达在信使RNA和蛋白质水平。此外，TLR 2缺陷显着抑制慢性吗啡诱导的原代神经元凋亡。吗啡处理后，TLR 2缺陷的原代神经元中caspase-3的活化受损。此外，吗啡处理未能诱导TLR 2缺陷的原代神经元中磷酸化糖原合成酶激酶3 β（GSK 3 β）水平的增加，表明GSK 3 β参与吗啡介导的TLR 2信号传导。因此，这些结果表明阿片类药物通过诱导TLR 2表达来引发神经元发生凋亡。我们的数据表明，抑制TLR 2能够防止阿片类药物诱导的神经元损伤。
Toll-like receptor 2 (TLR2), a key immune receptor in the TLR family, is widely expressed in various systems, including the immune and nervous systems and plays a critical role in controlling innate and adaptive immune responses. We previously reported that opioids inhibit cell growth and trigger apoptosis. However, the underlying mechanism by which TLR2 mediates apoptosis in response to opioids is not yet known. Here we show that chronic morphine treatment in primary neurons dramatically increased the expression of TLR2 at both the messenger RNA and protein levels. In addition, TLR2 deficiency significantly inhibited chronic morphine-induced apoptosis in primary neurons. Activation of caspase-3 after morphine treatment is impaired in TLR2 deficient primary neurons. Moreover, morphine treatment failed to induce an increased level of phosphorylated glycogen synthase kinase 3 beta (GSK3β) in TLR2 deficient primary neurons, suggesting an involvement of GSK3β in morphine-mediated TLR2 signaling. These results thus demonstrate that opioids prime neurons to undergo apoptosis by inducing TLR2 expression. Our data suggest that inhibition of TLR2 is capable of preventing opioids-induced damage to neurons.
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DOI：
10.1084/jem.191.8.1423
发表时间：
2000-04-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Yin D;Tuthill D;Mufson RA;Shi Y
通讯作者：
Shi Y
影响因子：
16.8
作者：
Fukao, T;Koyasu, S
通讯作者：
Koyasu, S
DOI：
10.1016/j.biocel.2007.10.006
发表时间：
2008-01-01
影响因子：
4
作者：
Lv, Xin;Su, Le;Miao, Junying
通讯作者：
Miao, Junying
影响因子：
5.3
作者：
Yakovlev, AG;Ota, K;Faden, AI
通讯作者：
Faden, AI
影响因子：
11.8
作者：
Sabroe, I;Dower, SK;Whyte, MKB
通讯作者：
Whyte, MKB