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Neurodegenerative and neuroprotective effects of tumor Necrosis factor (TNF) in retinal ischemia: opposite roles of TNF receptor 1 and TNF receptor 2.
J Neurosci. 2002 Apr 01; 22(7):RC216.JN

Abstract

Tumor necrosis factor (TNF) is an important factor in various acute and chronic neurodegenerative disorders. In retinal ischemia, we show early, transient upregulation of TNF, TNF receptor 1 (TNF-R1), and TNF-R2 6 hr after reperfusion preceding neuronal cell loss. To assess the specific role of TNF and its receptors, we compared ischemia-reperfusion-induced retinal damage in mice deficient for TNF-R1, TNF-R2, or TNF by quantifying neuronal cell loss 8 d after the insult. Surprisingly, TNF deficiency did not affect overall cell loss, yet absence of TNF-R1 led to a strong reduction of neurodegeneration and lack of TNF-R2 led to an enhancement of neurodegeneration, indicative of TNF-independent and TNF-dependent processes in the retina, with TNF-R1 augmenting neuronal death and TNF-R2 promoting neuroprotection. Western blot analyses of retinas revealed that reduction of neuronal cell loss in TNF-R1/ animals correlated with the presence of activated Akt/protein kinase B (PKB). Inhibition of the phosphatidylinositol 3-kinase signaling pathway reverted neuroprotection in TNF-R1-deficient mice, indicating an instrumental role of Akt/PKB in neuroprotection and TNF-R2 dependence of this pathway. Selective inhibition of TNF-R1 function may represent a new approach to reduce ischemia-induced neuronal damage, being potentially superior to strategies aimed at suppression of TNF activity in general.

Authors+Show Affiliations

Institute of Cell Biology and Immunology, University of Stuttgart, 70569 Stuttgart, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11917000

Citation

Fontaine, Valerie, et al. "Neurodegenerative and Neuroprotective Effects of Tumor Necrosis Factor (TNF) in Retinal Ischemia: Opposite Roles of TNF Receptor 1 and TNF Receptor 2." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, vol. 22, no. 7, 2002, pp. RC216.
Fontaine V, Mohand-Said S, Hanoteau N, et al. Neurodegenerative and neuroprotective effects of tumor Necrosis factor (TNF) in retinal ischemia: opposite roles of TNF receptor 1 and TNF receptor 2. J Neurosci. 2002;22(7):RC216.
Fontaine, V., Mohand-Said, S., Hanoteau, N., Fuchs, C., Pfizenmaier, K., & Eisel, U. (2002). Neurodegenerative and neuroprotective effects of tumor Necrosis factor (TNF) in retinal ischemia: opposite roles of TNF receptor 1 and TNF receptor 2. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 22(7), RC216.
Fontaine V, et al. Neurodegenerative and Neuroprotective Effects of Tumor Necrosis Factor (TNF) in Retinal Ischemia: Opposite Roles of TNF Receptor 1 and TNF Receptor 2. J Neurosci. 2002 Apr 1;22(7):RC216. PubMed PMID: 11917000.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neurodegenerative and neuroprotective effects of tumor Necrosis factor (TNF) in retinal ischemia: opposite roles of TNF receptor 1 and TNF receptor 2. AU - Fontaine,Valerie, AU - Mohand-Said,Saddek, AU - Hanoteau,Noelle, AU - Fuchs,Céline, AU - Pfizenmaier,Klaus, AU - Eisel,Ulrich, Y1 - 2002/03/25/ PY - 2002/3/28/pubmed PY - 2002/4/12/medline PY - 2002/3/28/entrez SP - RC216 EP - RC216 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience JO - J Neurosci VL - 22 IS - 7 N2 - Tumor necrosis factor (TNF) is an important factor in various acute and chronic neurodegenerative disorders. In retinal ischemia, we show early, transient upregulation of TNF, TNF receptor 1 (TNF-R1), and TNF-R2 6 hr after reperfusion preceding neuronal cell loss. To assess the specific role of TNF and its receptors, we compared ischemia-reperfusion-induced retinal damage in mice deficient for TNF-R1, TNF-R2, or TNF by quantifying neuronal cell loss 8 d after the insult. Surprisingly, TNF deficiency did not affect overall cell loss, yet absence of TNF-R1 led to a strong reduction of neurodegeneration and lack of TNF-R2 led to an enhancement of neurodegeneration, indicative of TNF-independent and TNF-dependent processes in the retina, with TNF-R1 augmenting neuronal death and TNF-R2 promoting neuroprotection. Western blot analyses of retinas revealed that reduction of neuronal cell loss in TNF-R1/ animals correlated with the presence of activated Akt/protein kinase B (PKB). Inhibition of the phosphatidylinositol 3-kinase signaling pathway reverted neuroprotection in TNF-R1-deficient mice, indicating an instrumental role of Akt/PKB in neuroprotection and TNF-R2 dependence of this pathway. Selective inhibition of TNF-R1 function may represent a new approach to reduce ischemia-induced neuronal damage, being potentially superior to strategies aimed at suppression of TNF activity in general. SN - 1529-2401 UR - https://www.unboundmedicine.com/medline/citation/11917000/Neurodegenerative_and_neuroprotective_effects_of_tumor_Necrosis_factor__TNF__in_retinal_ischemia:_opposite_roles_of_TNF_receptor_1_and_TNF_receptor_2_ L2 - http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=11917000 DB - PRIME DP - Unbound Medicine ER -