Trasmembrane chemokines CX3CL1 and CXCL16 drive interplay between neurons, microglia and astrocytes to counteract pMCAO and excitotoxic neuronal death.
Trasmembrane chemokines CX3CL1 and CXCL16 drive interplay between neurons, microglia and astrocytes to counteract pMCAO and excitotoxic neuronal death.
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Trasmembrane趋化因子CX3CL1和CXCL16在神经元，小胶质细胞和星形胶质细胞之间驱动相互作用，以抵消PMCAO和兴奋性神经元死亡。
DOI：
10.3389/fncel.2014.00193
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发表时间：
2014
影响因子：
5.3
通讯作者：
Trettel F
中科院分区：
文献类型：
--
作者：
Rosito M;Lauro C;Chece G;Porzia A;Monaco L;Mainiero F;Catalano M;Limatola C;Trettel F
在有害的损伤后，脑实质的细胞激活内源性自我保护机制以对抗脑损伤。小胶质细胞和星形胶质细胞之间的相互作用可以决定对损伤或应激引起的伤害性刺激的生理反应，因此了解小胶质细胞和星形胶质细胞之间的相互作用将有助于阐明胶质细胞在内源性保护机制中的作用，并可能有助于开发新的策略来动员这种程序并减少脑细胞死亡。在这里，我们证明了趋化因子CX3CL1和CXCL16是协同驱动神经元，小胶质细胞和星形胶质细胞之间的串扰，以促进生理神经保护机制，抵消由于缺血和兴奋性损伤的神经元细胞死亡的分子球员。在永久性大脑中动脉闭塞（pMCAO）的体内模型中，我们发现外源性施用可溶性CXCL 16减少缺血体积，并且在pMCAO后，内源性CXCL 16信号传导抑制脑损伤，在缺乏CXCL 16受体的小鼠中缺血体积减少。我们证明了作用于小胶质细胞的CX3CL1可促进CXCL16从胶质细胞中释放，这对于诱导神经保护作用是重要的，因为CXCL16信号传导的缺乏损害了CX3CL1对体外Glu兴奋性毒性损伤和pMCAO的神经保护作用。此外，腺苷受体A3R的活性和CCL 2的星形胶质细胞释放也在跨膜趋化因子神经保护作用中起作用，因为它们的失活降低了CX3CL 1和CXCL 16诱导的神经保护。
Upon noxious insults, cells of the brain parenchyma activate endogenous self-protective mechanisms to counteract brain damage. Interplay between microglia and astrocytes can be determinant to build a physiological response to noxious stimuli arisen from injury or stress, thus understanding the cross talk between microglia and astrocytes would be helpful to elucidate the role of glial cells in endogenous protective mechanisms and might contribute to the development of new strategy to mobilize such program and reduce brain cell death. Here we demonstrate that chemokines CX3CL1 and CXCL16 are molecular players that synergistically drive cross-talk between neurons, microglia and astrocytes to promote physiological neuroprotective mechanisms that counteract neuronal cell death due to ischemic and excitotoxic insults. In an in vivo model of permanent middle cerebral artery occlusion (pMCAO) we found that exogenous administration of soluble CXCL16 reduces ischemic volume and that, upon pMCAO, endogenous CXCL16 signaling restrains brain damage, being ischemic volume reduced in mice that lack CXCL16 receptor. We demonstrated that CX3CL1, acting on microglia, elicits CXCL16 release from glia and this is important to induce neroprotection since lack of CXCL16 signaling impairs CX3CL1 neuroprotection against both in vitro Glu-excitotoxic insult and pMCAO. Moreover the activity of adenosine receptor A3R and the astrocytic release of CCL2 play also a role in trasmembrane chemokine neuroprotective effect, since their inactivation reduces CX3CL1- and CXCL16 induced neuroprotection.
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影响因子：
5.3
作者：
Cipriani, Raffaela;Villa, Pia;Limatola, Cristina
通讯作者：
Limatola, Cristina
影响因子：
12.4
作者：
Boison, D.;Chen, J-F;Fredholm, B. B.
通讯作者：
Fredholm, B. B.
影响因子：
16.2
作者：
Bhaskar, Kiran;Konerth, Megan;Kokiko-Cochran, Olga N.;Cardona, Astrid;Ransohoff, Richard M.;Lamb, Bruce T.
通讯作者：
Lamb, Bruce T.
DOI：
10.1073/pnas.1111098109
发表时间：
2012-01-24
影响因子：
11.1
作者：
Pascual, Olivier;Ben Achour, Sarrah;Bessis, Alain
通讯作者：
Bessis, Alain
影响因子：
3.3
作者：
Catalano, Myriam;Lauro, Clotilde;Limatola, Cristina
通讯作者：
Limatola, Cristina