Nerve Growth Factor modulates LPS - induced microglial glycolysis and inflammatory responses.

Abstract:

:Microglia, the parenchymal immune cells of the central nervous system, orchestrate neuroinflammation in response to infection or damage, and promote tissue repair. However, aberrant microglial responses are integral to neurodegenerative diseases and critically contribute to disease progression. Thus, it is important to elucidate how microglia - mediated neuroinflammation is regulated by endogenous factors. Here, we explored the effect of Nerve Growth Factor (NGF), an abundant neurotrophin, on microglial inflammatory responses. NGF, via its high affinity receptor TrkA, downregulated LPS - induced production of pro-inflammatory cytokines and NO in primary mouse microglia and inhibited TLR4 - mediated activation of the NF-κB and JNK pathways. Furthermore, NGF attenuated the LPS - enhanced glycolytic activity in microglia, as suggested by reduced glucose uptake and decreased expression of the glycolytic enzymes Pfkβ3 and Ldhα. Consistently, 2DG - mediated glycolysis inhibition strongly downregulated LPS - induced cytokine production in microglial cells. Our findings demonstrate that NGF attenuates pro-inflammatory responses in microglia and may thereby contribute to regulation of microglia - mediated neuroinflammation.

journal_name

Exp Cell Res

authors

Fodelianaki G,Lansing F,Bhattarai P,Troullinaki M,Zeballos MA,Charalampopoulos I,Gravanis A,Mirtschink P,Chavakis T,Alexaki VI

doi

10.1016/j.yexcr.2019.02.023

subject

Has Abstract

pub_date

2019-04-15 00:00:00

pages

10-16

issue

1-2

eissn

0014-4827

issn

1090-2422

pii

S0014-4827(19)30088-6

journal_volume

377

pub_type

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