title: Blockade of CCR5 receptor prevents M2 microglia phenotype in a microglia-glioma paradigm.
abstract: 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 microglia-glioma interaction; the CCR5 blocker 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-1β 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.
authors.affiliation: Institute of Pharmacology, Catholic University Medical School, L.go F Vito 1, Rome, Italy.
authors.forename: Emilia
authors.initials: E
authors.lastname: Laudati
authors.affiliation: Institute of Pharmacology, Catholic University Medical School, L.go F Vito 1, Rome, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Currò
authors.affiliation: Institute of Pharmacology, Catholic University Medical School, L.go F Vito 1, Rome, Italy. Electronic address: pierluigi.navarra@unicatt.it.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Navarra
authors.affiliation: Institute of Pharmacology, Catholic University Medical School, L.go F Vito 1, Rome, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Lisi
mesh_terms: D000818:Animals; D065100:CCR5 Receptor Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D010641:Phenotype; D051381:Rats; D019713:Receptors, CCR5 / Q000378:metabolism*
chemical_list: D065100:CCR5 Receptor Antagonists; D019713:Receptors, CCR5
keywords: AKT; Arginase; Glioblastoma; Microglia; iNOS; mTOR