RT Journal Article
T1 CCL2/MCP-1 modulation of microglial activation and proliferation
A1 Hinojosa, Ara E.
A1 García Bueno, Borja
A1 Leza Cerro, Juan Carlos
A1 Muñoz Madrigal, José Luis
AB BackgroundMonocyte chemoattractant protein (CCL2/MCP-1) is a chemokine that attracts cells involved in the immune/inflammatory response. As microglia are one of the main cell types sustaining inflammation in brain, we proposed here to analyze the direct effects of MCP-1 on cultured primary microglia.MethodsPrimary microglia and neuronal cultures were obtained from neonatal and embryonic Wistar rats, respectively. Microglia were incubated with different concentrations of recombinant MCP-1 and LPS. Cell proliferation was quantified by measuring incorporation of bromodeoxyuridine (BrdU). Nitrite accumulation was measured using the Griess assay. The expression and synthesis of different proteins was measured by RT-PCR and ELISA. Cell death was quantified by measuring release of LDH into the culture medium.ResultsMCP-1 treatment (50 ng/ml, 24 h) did not induce morphological changes in microglial cultures. Protein and mRNA levels of different cytokines were measured, showing that MCP-1 was not able to induce proinflammatory cytokines (IL-1β, IL6, MIP-1α), either by itself or in combination with LPS. A similar lack of effect was observed when measuring inducible nitric oxide synthase (NOS2) expression or accumulation of nitrites in the culture media as a different indicator of microglial activation. MCP-1 was also unable to alter the expression of different trophic factors that were reduced by LPS treatment. In order to explore the possible release of other products by microglia and their potential neurotoxicity, neurons were co-cultured with microglia: no death of neurons could be detected when treated with MCP-1. However, the presence of MCP-1 induced proliferation of microglia, an effect opposite to that observed with LPS.ConclusionThese data indicate that, while causing migration and proliferation of microglia, MCP-1 does not appear to directly activate an inflammatory response in this cell type, and therefore, other factors may be necessary to cause the changes that result in the neuronal damage commonly observed in situations where MCP-1 levels are elevated.
PB Springer Nature
SN 1742-2094
YR 2011
FD 2011-07-05
LK https://hdl.handle.net/20.500.14352/134298
UL https://hdl.handle.net/20.500.14352/134298
LA eng
NO Hinojosa, A.E., Garcia-Bueno, B., Leza, J.C. et al. CCL2/MCP-1 modulation of microglial activation and proliferation. J Neuroinflammation 8, 77 (2011). https://doi.org/10.1186/1742-2094-8-77
NO Ministerio de Ciencia e Innovación (España)
NO Centro de Investigación en Red de Salud Mental
DS Docta Complutense
RD 18 abr 2026