Proinflammatory-activated glioma cells induce a switch in microglial polarization and activation status, from a predominant M2b phenotype to a mixture of M1 and M2a/B polarized cells

Lucia Lisi, Egidio Stigliano, Libero Lauriola, Pierluigi Navarra, Cinzia Dello Russo*

*Autore corrispondente per questo lavoro

Risultato della ricerca: Contributo in rivistaArticolo

45 Citazioni (Scopus)

Abstract

Malignant gliomas are primary brain tumors characterized by morphological and genetic complexities, aswell as diffuse infiltration into normal brain parenchyma. Within gliomas, microglia/ macrophages represent the largest tumor-infiltrating cell population, contributing by at least one-third to the total tumor mass. Bi-directional interactions between glioma cells and microglia may therefore play an important role on tumor growth and biology. In the present study, we have characterized the influence of glioma-soluble factors on microglial function, comparing the effects of media harvested under basal conditions with those of media obtained after inducing a pro-inflammatory activation state in glioma cells. We found that microglial cells undergo a different pattern of activation depending on the stimulus; in the presence of activated glioma-derived factors, i.e. a condition mimicking the late stage of pathology, microglia presents as a mixture of polarization phenotypes (M1 and M2a/b), with up-regulation of iNOS (inducible nitric oxide synthase), ARG (arginase) and IL (interleukine)-10. At variance, microglia exposed to basal glioma-derived factors, i.e. a condition resembling the early stage of pathology, shows a more specific pattern of activation, with increased M2b polarization status and upregulation of IL-10 only. As far as viability and cell proliferation are concerned, both LI-CM [LPS (lipopolysaccharide)- IFNγ (interferon γ) conditioned media] and C-CM (controlconditioned media) induce similar effects on microglial morphology. Finally, in human glioma tissue obtained from surgical resection of patients with IV grade glioblastoma, we detected a significant amount of CD68 positive cells, which is a marker of macrophage/microglial phagocytic activity, suggesting that in vitro findings presented here might have a relevance in the human pathology as well. © 2014 The Author(s).
Lingua originaleInglese
pagine (da-a)171-183
Numero di pagine13
RivistaASN Neuro
Volume6
DOI
Stato di pubblicazionePubblicato - 2014

Keywords

  • Animals
  • Animals, Newborn
  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Arginase
  • Cell Proliferation
  • Cells, Cultured
  • Cerebral Cortex
  • Culture Media, Conditioned
  • Dose-Response Relationship, Drug
  • Glioma
  • Humans
  • IL-10
  • Interferon-gamma
  • Lipopolysaccharides
  • Medicine (all)
  • Microglia
  • Microglial polarization
  • NOS
  • Neuroglia
  • Neurology (clinical)
  • Neuroscience (all)
  • Nitric Oxide Synthase Type II
  • Phenotype
  • Rats
  • Time Factors
  • Up-Regulation
  • mTOR

Fingerprint

Entra nei temi di ricerca di 'Proinflammatory-activated glioma cells induce a switch in microglial polarization and activation status, from a predominant M2b phenotype to a mixture of M1 and M2a/B polarized cells'. Insieme formano una fingerprint unica.

Cita questo