Prostaglandin E2 released from activated microglia enhances astrocyte proliferation in vitro.
Prostaglandin E2 released from activated microglia enhances astrocyte proliferation in vitro.
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DOI：
10.1016/j.taap.2009.04.015
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发表时间：
2009-07-01
影响因子：
3.8
通讯作者：
Hong JS
中科院分区：
文献类型：
--
作者：
Zhang D;Hu X;Qian L;Wilson B;Lee C;Flood P;Langenbach R;Hong JS
小胶质细胞活化与包括星形胶质瘤在内的许多星形胶质细胞病相关的病理条件有关;然而，详细的机制尚不清楚。在这项研究中，我们使用原代富集的小胶质细胞和星形胶质细胞培养物，以确定小胶质细胞前列腺素E2（PGE 2）在星形胶质细胞增殖中的作用。用BrdU掺入法检测星形胶质细胞增殖情况。采用ELISA法测定PGE 2水平。本研究还应用药物抑制或基因消融小胶质细胞中的考克斯-2。我们发现，在小胶质细胞存在下，脂多糖（LPS）处理后星形胶质细胞的增殖增加。此外，在LPS处理的小胶质细胞的条件培养基的存在下，观察到星形胶质细胞的增殖增加。LPS处理可增加小胶质细胞中PGE 2的产生和考克斯-2的表达，提示小胶质细胞PGE 2可能参与了星形胶质细胞增殖的增强。此外，激活的小胶质细胞诱导的星形胶质细胞增殖的增加被PGE 2拮抗剂AH 6809、考克斯-2选择性抑制剂DuP-697或小胶质细胞考克斯-2的基因敲除阻断。这些发现进一步得到了向培养基中添加PGE 2显著诱导星形胶质细胞增殖的发现的支持。这些结果表明，小胶质细胞PGE 2在星形胶质细胞增殖中起着重要作用，将PGE 2鉴定为触发与不可控制的星形胶质细胞增殖相关的病理反应的关键神经炎性分子。这些研究结果是重要的，在阐明活化的小胶质细胞和PGE 2在星形胶质细胞增殖的作用，并建议在使用抗炎剂治疗星形胶质细胞瘤的潜在途径。
Microglial activation has been implicated in many astrogliosis-related pathological conditions including astroglioma; however, the detailed mechanism is not clear. In this study, we used primary enriched microglia and astrocytes cultures to determine the role of microglial prostaglandin E2 (PGE2) in the proliferation of astrocytes. The proliferation of astrocytes was measured by BrdU incorporation. The level of PGE2 was measured by ELISA method. Pharmacological inhibition or genetic ablation of COX-2 in microglia were also applied in this study. We found that proliferation of astrocytes increased following lipopolysaccharide (LPS) treatment in the presence of microglia. Furthermore, increased proliferation of astrocytes was observed in the presence of conditioned media from LPS-treated microglia. The potential involvement of microglial PGE2 in enhanced astrocyte proliferation was suggested by the findings that PGE2 production and COX-2 expression in microglia were increased by LPS treatment. In addition, activated microglia-induced increases in astrocyte proliferation were blocked by the PGE2 antagonist AH6809, COX-2 selective inhibitor DuP-697 or by genetic knockout of microglial COX-2. These findings were further supported by the finding that addition of PGE2 to the media significantly induced astrocyte proliferation. These results indicate that microglial PGE2 plays an important role in astrocyte proliferation, identifying PGE2 as a key neuroinflammatory molecule that triggers the pathological response related to uncontrollable astrocyte proliferation. These findings are important in elucidating the role of activated microglia and PGE2 in astrocyte proliferation and in suggesting a potential avenue in the use of anti-inflammatory agents for the therapy of astroglioma.
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DOI：
10.1016/s0165-3806(03)00190-1
发表时间：
2003-10-10
期刊：
DEVELOPMENTAL BRAIN RESEARCH
影响因子：
--
作者：
Douhou, A;Debeir, T;Raisman-Vozari, R
通讯作者：
Raisman-Vozari, R
影响因子：
3.4
作者：
Iravani, MM;Leung, CCM;Jenner, P
通讯作者：
Jenner, P
DOI：
10.1124/jpet.102.043166
发表时间：
2003-04-01
影响因子：
3.5
作者：
Liu, YX;Qin, LY;Hong, JS
通讯作者：
Hong, JS
影响因子：
6.2
作者：
Herber, DL;Maloney, JL;Gordon, MN
通讯作者：
Gordon, MN
影响因子：
12.7
作者：
Haga, S;Haga, C;Ikeda, K
通讯作者：
Ikeda, K