S100B attenuates microglia activation in gliomas: possible role of STAT3 pathway.
S100B attenuates microglia activation in gliomas: possible role of STAT3 pathway.
复制标题
DOI：
10.1002/glia.21118
复制
发表时间：
2011-03
期刊：
影响因子：
6.2
通讯作者：
Badie, Behnam
中科院分区：
文献类型：
--
作者：
Zhang, Leying;Liu, Wei;Alizadeh, Darya;Zhao, Dongchang;Farrukh, Omar;Lin, Jeffrey;Badie, Sam A.;Badie, Behnam
尽管巨噬细胞（MPs）和小胶质细胞（MG）的效应功能在胶质瘤中明显受到抑制。尽管STAT3通路被认为在这一过程中起作用，但胶质瘤诱导MPs和MG中STAT3激活的确切机制尚不清楚。由于晚期糖基化终产物受体（RAGE）的激活可以诱导STAT3，并且由于胶质瘤表达高水平的RAGE配体S100B，我们假设MP/MG STAT3活性可能通过S100B-RAGE相互作用被调节。将N9 MG和骨髓源性单核细胞（BMM）暴露于GL261胶质瘤条件中（GCM）和低（nM）水平的S100B中，可增加RAGE表达，诱导STAT3并抑制MG的体外功能。此外，GCM中S100B的中和部分逆转了BMM中IL-1β的抑制，这表明GCM的抑制作用部分是由于S100B。最后，阻断S100B-RAGE相互作用抑制STAT3在N9 MG和胶质瘤MG/MP中的激活。这些发现表明RAGE通路可能在STAT3诱导胶质瘤相关MG/MPs中发挥重要作用，并且该过程可能通过S100B介导。
Despite significant infiltration into tumors, the effector function of macrophages (MPs) and microglia (MG) appears to be suppressed in gliomas. Although STAT3 pathway is thought to play a role in this process, the exact mechanism by which gliomas induce STAT3 activation in MPs and MG is not known. Because activation of receptor for advanced glycation end products (RAGE) can induce STAT3, and because gliomas express high levels of S100B, a RAGE ligand, we hypothesized that MP/MG STAT3 activity may be modulated through S100B-RAGE interaction. Exposure of N9 MG and bone marrow-derived monocytes (BMM) to GL261 glioma condition medium (GCM) and low (nM) levels of S100B increased RAGE expression, induced STAT3 and suppressed MG function in vitro. Furthermore, neutralization of S100B in GCM, partially reversed IL-1β suppression in BMM, suggesting that the inhibitory effect of GCM to be in part due to S100B. Finally, blockage of S100B-RAGE interaction inhibited STAT3 activation in N9 MG and in glioma MG/MP in vivo. These findings suggest that the RAGE pathway may play an important role in STAT3 induction in glioma-associated MG/MPs, and that this process may be mediated through S100B.
登录
查看更多内容
影响因子：
3.3
作者：
Edwards, M. M.;Robinson, S. R.
通讯作者：
Robinson, S. R.
影响因子：
11.2
作者：
Hussain, S. Farzana;Kong, Ling-Yuan;Heimberger, Amy B.
通讯作者：
Heimberger, Amy B.
影响因子：
3.9
作者：
Bassi, Rosaria;Giussani, Paola;Riboni, Laura
通讯作者：
Riboni, Laura
影响因子：
5.5
作者：
Bianchi, Roberta;Adami, Cecilia;Donato, Rosario
通讯作者：
Donato, Rosario
影响因子：
4
作者：
Fasshauer, M;Kralisch, S;Paschke, R
通讯作者：
Paschke, R