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

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

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.

Details

OriginalspracheEnglisch
Seiten (von - bis)10-16
Seitenumfang7
FachzeitschriftExperimental cell research
Jahrgang377
Ausgabenummer1-2
PublikationsstatusVeröffentlicht - 15 Apr. 2019
Peer-Review-StatusJa

Externe IDs

Scopus 85062192498
ORCID /0000-0001-9335-9749/work/142256399

Schlagworte

Schlagwörter

  • Animals, Cytokines/genetics, Glycolysis/drug effects, Inflammation/chemically induced, Lipopolysaccharides/toxicity, Mice, Mice, Inbred C57BL, Microglia/drug effects, NF-kappa B/genetics, Nerve Growth Factor/pharmacology, Signal Transduction

Bibliotheksschlagworte