Interleukin-1β Enhances NMDA Receptor-Mediated Intracellular Calcium Increase through Activation of the Src Family of Kinases
Abstract
Interleukin (IL)-1β is a proinflammatory cytokine implicated in various pathophysiological conditions of the CNS involving NMDA receptor activation. Circumstantial evidence suggests that IL-1β and NMDA receptors can functionally interact. Using primary cultures of rat hippocampal neurons, we investigated whether IL-1β affects NMDA receptor function(s) by studying (1) NMDA receptor-induced [Ca 2+]i increase and (2) NMDA-mediated neurotoxicity. IL1β (0.01-0.1 ng/ml) dose-dependently enhances NMDA-induced [Ca 2+]i increases with a maximal effect of ∼45%. This effect occurred only when neurons were pretreated with IL-1β, whereas it was absent if IL-1β and NMDA were applied simultaneously, and it was abolished by IL-1 receptor antagonist (50 ng/ml). Facilitation of NMDA-induced [Ca 2+]i increase by IL-1β was prevented by both lavendustin (LAV) A (500 n m) and 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2) (1 μ m), suggesting an involvement of tyrosine kinases. Increased tyrosine phosphorylation of NMDA receptor subunits 2A and 2B and coimmunoprecipitation of activated Src tyrosine kinase with these subunits was observed after exposure of hippocampal neurons to 0.05 ng/ml IL-1β. Finally, 0.05 ng/ml IL-1β increased by ∼30% neuronal cell death induced by NMDA, and this effect was blocked by both lavendustin A and PP2. These data suggest that IL-1β increases NMDA receptor function through activation of tyrosine kinases and subsequent NR2A/B subunit phosphorylation. These effects may contribute to glutamate-mediated neurodegeneration.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Inflammatory cytokines TNF-α and IL-1β play a critical role in chronic neuroinflammatory disorders by modulating the expression and/or properties of synaptic channels.
“inflammatory cytokines, i.e. TNF-α and IL-1β, play a critical role in chronic neuroinflammatory disorders, by modulating the expression and/or properties of synaptic channels”
From Glia-to-neuron transfer of miRNAs via extracellular vesicles: a new mechanism underlying inflammation-induced synaptic alterations (2018) · cites this paper as [79]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Extrasynaptic NMDARs oppose synaptic NMDARs by triggering CREB shut-off and cell death pathways
Hardingham, G. E., Fukunaga, Y., & Bading, H. (2002) · Nature Neuroscience · doi:10.1038/nn835 · Cited by 1,686 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The role of inflammation in epilepsy
Vezzani, A., French, J., Bartfai, T., & Baram, T. Z. (2011) · Nature Reviews Neurology · doi:10.1038/nrneurol.2010.178 · Cited by 1,876 · see citing works
Self-citationImmune modulation of learning, memory, neural plasticity and neurogenesis
Yirmiya, R., & Goshen, I. (2011) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2010.10.015 · Cited by 1,483 · see citing works
Blood–brain barrier breakdown as a therapeutic target in traumatic brain injury
Shlosberg, D., Benifla, M., Kaufer, D., & Friedman, A. (2010) · Nature Reviews Neurology · doi:10.1038/nrneurol.2010.74 · Cited by 897 · see citing works
Austin, P. J., & Moalem-Taylor, G. (2010) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2010.08.013 · Cited by 607 · see citing works
Immune–neural connections: how the immune system’s response to infectious agents influences behavior
McCusker, R. H., & Kelley, K. W. (2013) · Journal of Experimental Biology · doi:10.1242/jeb.073411 · Cited by 429 · see citing works
Zhong, L., Xu, Y., Zhuo, R., Wang, T., Wang, K., Huang, R., Wang, D., Gao, Y., Zhu, Y., Sheng, X., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09118-9 · Cited by 371 · see citing works
Paudel, Y. N., Shaikh, M. F., Chakraborti, A., Kumari, Y., Aledo-Serrano, Á., Aleksovska, K., Alvim, M. K. M., & Othman, I. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00628 · Cited by 311 · see citing works
Prada, I., Gabrielli, M., Turola, E., Iorio, A., D’Arrigo, G., Parolisi, R., De Luca, M., Pacifici, M., Bastoni, M., Lombardi, M., et al. (2018) · Acta Neuropathologica · doi:10.1007/s00401-017-1803-x · Cited by 312 · see citing works
Tong, L., Prieto, G. A., Kramár, E. A., Smith, E. D., Cribbs, D. H., Lynch, G., & Cotman, C. W. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.1253-12.2012 · Cited by 254 · see citing works
Seizure-induced brain-borne inflammation sustains seizure recurrence and blood-brain barrier damage
Librizzi, L., Noè, F., Vezzani, A., de Curtis, M., & Ravizza, T. (2012) · Annals of Neurology · doi:10.1002/ana.23567 · Cited by 253 · see citing works
Self-citationMechanisms of neuroimmune gene induction in alcoholism
Crews, F. T., & Vetreno, R. P. (2016) · Psychopharmacology · doi:10.1007/s00213-015-3906-1 · Cited by 232 · see citing works
Interleukin-1β impairs brain derived neurotrophic factor-induced signal transduction
Tong, L., Balazs, R., Soiampornkul, R., Thangnipon, W., & Cotman, C. W. (2008) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.02.027 · Cited by 222 · see citing works
Watkins, L. R., Hutchinson, M. R., Milligan, E. D., & Maier, S. F. (2007) · Brain Research Reviews · doi:10.1016/j.brainresrev.2007.06.006 · Cited by 185 · see citing works
Arrode-Brusés, G., & Brusés, J. L. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-83 · Cited by 146 · see citing works
Shao, S., Xu, C.-B., Chen, C.-J., Shi, G.-N., Guo, Q.-L., Zhou, Y., Wei, Y.-Z., Wu, L., Shi, J.-G., & Zhang, T.-T. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02178-z · Cited by 112 · see citing works
Neuroimmune regulation of homeostatic synaptic plasticity
Pribiag, H., & Stellwagen, D. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.06.008 · Cited by 106 · see citing works
The effects of ozone exposure and associated injury mechanisms on the central nervous system
Martínez-Lazcano, J. C., González-Guevara, E., del Carmen Rubio, M., Franco-Pérez, J., Custodio, V., Hernández-Cerón, M., Livera, C., & Paz, C. (2013) · Reviews in the Neurosciences · doi:10.1515/revneuro-2012-0084 · Cited by 94 · see citing works
Ataka, K., Asakawa, A., Nagaishi, K., Kaimoto, K., Sawada, A., Hayakawa, Y., Tatezawa, R., Inui, A., & Fujimiya, M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0081744 · Cited by 89 · see citing works
Visceral Inflammation and Immune Activation Stress the Brain
Holzer, P., Farzi, A., Hassan, A. M., Zenz, G., Jačan, A., & Reichmann, F. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01613 · Cited by 84 · see citing works
Orellana, D. I., Quintanilla, R. A., Gonzalez-Billault, C., & Maccioni, R. B. (2005) · Neurotoxicity Research · doi:10.1007/bf03033983 · Cited by 76 · see citing works
Schmid, A. W., Lynch, M. A., & Herron, C. E. (2009) · Hippocampus · doi:10.1002/hipo.20542 · Cited by 64 · see citing works
Hridi, S. U., Franssen, A. J. P. M., Jiang, H.-R., & Bushell, T. J. (2019) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2019.01.002 · Cited by 20 · see citing works
- Authors
- Viviani, B., Bartesaghi, S., Gardoni, F., Vezzani, A., Behrens, M. M., Bartfai, T., Binaglia, M., Corsini, E., Di Luca, M., Galli, C. L., & Marinovich, M.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2003-09-24
- Volume
- 23
- Issue
- 25
- Pages
- 8692-8700
- ISSN
- 0270-6474
- 1529-2401
- Cited by
- 876
- References
- 1
- Language
- en
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
