Blockade of CCR5 receptor prevents M2 microglia phenotype in a microglia-glioma paradigm

被引:49
作者
Laudati, Emilia [1 ]
Curro, Diego [1 ]
Navarra, Pierluigi [1 ]
Lisi, Lucia [1 ]
机构
[1] Catholic Univ, Inst Pharmacol, Med Sch, Lgo F Vito 1, Rome, Italy
关键词
Microglia; Glioblastoma; iNOS; Arginase; ART; mTOR; GLIOBLASTOMA CELLS; IN-VITRO; CHEMOKINE; INVASION; POLARIZATION; M1; INHIBITION; MECHANISMS; CANCER; BRAIN;
D O I
10.1016/j.neuint.2017.03.002
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Microglia express chemokines and their cognate receptors that were found to play important roles in many processes required for tumor development, such as tumor growth, proliferation, invasion, and angiogenesis. Among the chemokine receptor, CCR5 have been documented in different cancer models; in particular, CCR5 is highly expressed in human glioblastoma, where it is associated to poor prognosis. In the present study, we investigated the effect of CCR5 receptor blockade on a paradigm of microgliaglioma interaction; the CCR5 blacker maraviroc (MRV) was used as a pharmacological tool. We found that MVR is able to reduce the gene expression and function of the M2 markers ARG1 and IL-10 in presence of both basal glioma-released factors (C-CM) and activated glioma-released factors (LI-CM), but it up-regulates the M1 markers NO and IL-1 beta only if microglia is stimulated by LI-CM; the latter effect appears to be mediated by the inhibition of mTOR pathway. In addition, CCR5 blockade was associated to a significant reduction in microglia migration, an effect mediated through the inhibition of AKT pathway. (C) 2017 Elsevier Ltd. All rights reserved.
引用
收藏
页码:100 / 108
页数:9
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