SciELO - Scientific Electronic Library Online

 
vol.50TMPYP4 exerted antitumor effects in human cervical cancer cells through activation of p38 mitogen-activated protein kinaseThe comparative mitogenomics and phylogenetics of the two grouse-grasshoppers (Insecta, Orthoptera, Tetrigoidea) author indexsubject indexarticles search
Home Pagealphabetic serial listing  

Services on Demand

Journal

Article

Indicators

Related links

  • On index processCited by Google
  • Have no similar articlesSimilars in SciELO
  • On index processSimilars in Google

Share


Biological Research

Print version ISSN 0716-9760

Abstract

ZHANG, Li et al. Neuron-derived CCL2 contributes to microglia activation and neurological decline in hepatic encephalopathy. Biol. Res. [online]. 2017, vol.50, 26.  Epub Oct 30, 2017. ISSN 0716-9760.  http://dx.doi.org/10.1186/s40659-017-0130-y.

Background

CCL2 was up-regulated in neurons and involved in microglia activation and neurological decline in mice suffering from hepatic encephalopathy (HE). However, no data exist concerning the effect of neuron-derived CCL2 on microglia activation in vitro.

Methods

The rats were pretreated with CCL2 receptor inhibitors (INCB or C021, 1 mg/kg/day i.p.) for 3 days prior to thioacetamide (TAA) administration (300 mg/kg/day i.p.) for inducing HE model. At 8 h following the last injection (and every 4 h after), the grade of encephalopathy was assessed. Blood and whole brains were collected at coma for measuring CCL2 and Iba1 expression. In vitro, primary neurons were stimulated with TNF-α, and then the medium were collected for addition to microglia cultures with or without INCB or C021 pretreatment. The effect of the medium on microglia proliferation and activation was evaluated after 24 h.

Results

CCL2 expression and microglia activation were elevated in the cerebral cortex of rats received TAA alone. CCL2 receptors inhibition improved neurological score and reduced cortical microglia activation. In vitro, TNF-α treatment induced CCL2 release by neurons. Medium from TNF-α stimulated neurons caused microglia proliferation and M1 markers expression, including iNOS, COX2, IL-6 and IL-1β, which could be suppressed by INCB or C021 pretreatment. The medium could also facilitate p65 nuclear translocation and IκBα phosphorylation, and NF-κB inhibition reduced the increased IL-6 and IL-1β expression induced by the medium.

Conclusion

Neuron-derived CCL2 contributed to microglia activation and neurological decline in HE. Blocking CCL2 or inhibiting microglia excessive activation may be potential strategies for HE.

Keywords : Hepatic encephalopathy; Neuron; Microglia; Chemokine CC motif ligand 2.

        · text in English     · English ( pdf )