Inflammatory cytokines IL-1β and TNF-α regulate p75 NTR expression in CNS neurons and astrocytes by distinct celltype-specific signalling mechanisms

Soyoung Choi, Wilma J. Friedman

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

The p75NTR (where NTR is neurotrophin receptor) can mediate many distinct cellular functions, including cell survival and apoptosis, axonal growth and cell proliferation, depending on the cellular context. This multifunctional receptor is widely expressed in the CNS (central nervous system) during development, but its expression is restricted in the adult brain. However, p75NTR is induced by a variety of pathophysiological insults, including seizures, lesions and degenerative disease. We have demonstrated previously that p75NTR is induced by seizures in neurons, where it induces apoptosis, and in astrocytes, where it may regulate proliferation. In the present study, we have investigated whether the inflammatory cytokines IL (interleukin)-1β and TNF-α (tumour necrosis factor-α), that are commonly elevated in these pathological conditions, mediate the regulation of p75NTR in neurons and astrocytes. We have further analysed the signal transduction pathways by which these cytokines induce p75NTR expression in the different cell types, specifically investigating the roles of the NF-κB (nuclear factor κB) and p38 MAPK (mitogen-activated protein kinase) pathways. We have demonstrated that both cytokines regulate p75NTR expression; however, the mechanisms governing this regulation are cytokine- and cell-type specific. The distinct mechanisms of cytokine-mediated p75NTR regulation that we demonstrate in the present study may facilitate therapeutic intervention in regulation of this receptor in a cell-selective manner.

Original languageEnglish (US)
Article numbere00010
Pages (from-to)113-123
Number of pages11
JournalASN neuro
Volume1
Issue number2
DOIs
StatePublished - 2009

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Clinical Neurology

Keywords

  • Neurotrophin receptor
  • Nuclear factor κB (NF-κB)
  • P38 mitogen-activated protein kinase (p38 MAPK)

Fingerprint

Dive into the research topics of 'Inflammatory cytokines IL-1β and TNF-α regulate p75 <sup>NTR</sup> expression in CNS neurons and astrocytes by distinct celltype-specific signalling mechanisms'. Together they form a unique fingerprint.

Cite this