Interleukin-1beta interferes with signal transduction induced by neurotrophin-3 in cortical neurons.
It was previously observed that IL-1beta interferes with BDNF-induced TrkB-mediated signal transduction and protection of cortical neurons from apoptosis evoked by deprivation from trophic support [Tong L., Balazs R., Soiampornkul R., Thangnipon W., Cotman C.W., 2007. Interleukin-1beta impairs brain derived neurotrophic factor-induced signal transduction. Neurobiol. Aging]. Here we investigated whether the effect of the cytokine on neurotrophin signaling is more general. The influence of IL-1beta on NT-3 signaling was therefore studied under conditions when NT-3 primarily activated the TrkC receptor. The cytokine reduced NT-3-induced activation of MAPK/ERK and Akt, but did not interfere with Trk receptor autophosphorylation. IL-1beta reduced tyrosine phosphorylation of the docking proteins, IRS-1 and Shc, which convey receptor activation to the downstream protein kinase cascades. These are the steps that are also inhibited by IL-1beta in BDNF-induced signal transduction. The functional consequences of the effect of IL-1beta on NT-3 signaling were severe, as NT-3 protection of the trophic support-deprived cortical neurons was abrogated. In view of the role in the maintenance and plasticity of neurons of ERK, Akt and CREB, which are activated by neurotrophins, elevated IL-1beta levels in the brain in Alzheimer's disease and other neurodegenerative diseases might contribute to the decline in cognitive functions before the pathological signs of the disease develop.
Neuro-Behavioral Biology Center, Institute of Science and Technology for Development, Mahidol University, Salaya Campus Nakorn Pathom, Thailand.
Rungtip
R
Soiampornkul
Liqi
L
Tong
Wipawan
W
Thangnipon
Robert
R
Balazs
Carl W
CW
Cotman
D048868:Adaptor Proteins, Signal Transducing / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins; D053583:Interleukin-1beta / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D009410:Nerve Degeneration / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D019636:Neurodegenerative Diseases / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D020933:Neurotrophin 3 / Q000187:drug effects / Q000378:metabolism*; D051058:Oncogene Protein v-akt / Q000378:metabolism; D051381:Rats; D020812:Receptor, trkC / Q000819:agonists / Q000378:metabolism; D055765:Shc Signaling Adaptor Proteins; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1
D048868:Adaptor Proteins, Signal Transducing; D017362:Cyclic AMP Response Element-Binding Protein; D055504:Insulin Receptor Substrate Proteins; D053583:Interleukin-1beta; C526296:Irs1 protein, rat; D020933:Neurotrophin 3; D055765:Shc Signaling Adaptor Proteins; C528035:Shc1 protein, rat; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D020812:Receptor, trkC; D051058:Oncogene Protein v-akt; D048049:Extracellular Signal-Regulated MAP Kinases