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Interleukin-1 receptor associated kinases-1/4 inhibition protects against acute hypoxia/ischemia-induced neuronal injury in vivo and in vitro.
Neuroscience. 2011 Nov 24; 196:25-34.N

Abstract

Neuronal Toll-like receptors (TLRs)-2 and -4 have been shown to play a pivotal role in ischemic brain injury, and the interleukin-1 receptor associated kinases (IRAKs) are considered to be the key signaling molecules involved downstream of TLRs. Here, we investigated the expression levels of IRAK-1 and -4 and the effects of IRAK-1/4 inhibition on brain ischemic insult and neuronal hypoxia-induced injury. Male Sprague-Dawley (SD) rats and the rat neuroblastoma B35 cell line were used in these experiments. Permanent middle cerebral artery occlusion (MCAO) was induced by the intraluminal filament technique, and B35 cells were stimulated with the hypoxia-mimetic, cobalt chloride (CoCl(2)). Following induction of hypoxia/ischemia (H/I), B35 cells and cerebral cortical neurons expressed higher levels of IRAK-1 and -4. Furthermore, IRAK-1/4 inhibition decreased the mortality rate, functional deficits, and ischemic infarct volume by 7 days after MCAO. Similarly, IRAK-1/4 inhibition attenuated CoCl(2)-induced cytotoxicity and apoptosis in B35 cells in vitro. Our results show that IRAK-1/4 inhibition decreased the nuclear translocation of the nuclear factor-kappaB (NF-κB) p65 subunit, the levels of activated (phosphorylated) c-jun N-terminal kinase (JNK) and cleaved caspase-3, and the secretion of TNF-α and IL-6 in B35 cells at 6 h after CoCl(2) treatment. These data suggest that IRAK-1/4 inhibition plays a neuroprotective role in H/I-induced brain injury.

Authors+Show Affiliations

Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Gaotanyan 30, Chongqing 400038, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo 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

21925238

Citation

Yang, Y-F, et al. "Interleukin-1 Receptor Associated Kinases-1/4 Inhibition Protects Against Acute Hypoxia/ischemia-induced Neuronal Injury in Vivo and in Vitro." Neuroscience, vol. 196, 2011, pp. 25-34.
Yang YF, Chen Z, Hu SL, et al. Interleukin-1 receptor associated kinases-1/4 inhibition protects against acute hypoxia/ischemia-induced neuronal injury in vivo and in vitro. Neuroscience. 2011;196:25-34.
Yang, Y. F., Chen, Z., Hu, S. L., Hu, J., Li, B., Li, J. T., Wei, L. J., Qian, Z. M., Lin, J. K., Feng, H., & Zhu, G. (2011). Interleukin-1 receptor associated kinases-1/4 inhibition protects against acute hypoxia/ischemia-induced neuronal injury in vivo and in vitro. Neuroscience, 196, 25-34. https://doi.org/10.1016/j.neuroscience.2011.08.059
Yang YF, et al. Interleukin-1 Receptor Associated Kinases-1/4 Inhibition Protects Against Acute Hypoxia/ischemia-induced Neuronal Injury in Vivo and in Vitro. Neuroscience. 2011 Nov 24;196:25-34. PubMed PMID: 21925238.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interleukin-1 receptor associated kinases-1/4 inhibition protects against acute hypoxia/ischemia-induced neuronal injury in vivo and in vitro. AU - Yang,Y-F, AU - Chen,Z, AU - Hu,S-L, AU - Hu,J, AU - Li,B, AU - Li,J-T, AU - Wei,L-J, AU - Qian,Z-M, AU - Lin,J-K, AU - Feng,H, AU - Zhu,G, Y1 - 2011/09/10/ PY - 2011/05/19/received PY - 2011/08/23/revised PY - 2011/08/25/accepted PY - 2011/9/20/entrez PY - 2011/9/20/pubmed PY - 2012/2/24/medline SP - 25 EP - 34 JF - Neuroscience JO - Neuroscience VL - 196 N2 - Neuronal Toll-like receptors (TLRs)-2 and -4 have been shown to play a pivotal role in ischemic brain injury, and the interleukin-1 receptor associated kinases (IRAKs) are considered to be the key signaling molecules involved downstream of TLRs. Here, we investigated the expression levels of IRAK-1 and -4 and the effects of IRAK-1/4 inhibition on brain ischemic insult and neuronal hypoxia-induced injury. Male Sprague-Dawley (SD) rats and the rat neuroblastoma B35 cell line were used in these experiments. Permanent middle cerebral artery occlusion (MCAO) was induced by the intraluminal filament technique, and B35 cells were stimulated with the hypoxia-mimetic, cobalt chloride (CoCl(2)). Following induction of hypoxia/ischemia (H/I), B35 cells and cerebral cortical neurons expressed higher levels of IRAK-1 and -4. Furthermore, IRAK-1/4 inhibition decreased the mortality rate, functional deficits, and ischemic infarct volume by 7 days after MCAO. Similarly, IRAK-1/4 inhibition attenuated CoCl(2)-induced cytotoxicity and apoptosis in B35 cells in vitro. Our results show that IRAK-1/4 inhibition decreased the nuclear translocation of the nuclear factor-kappaB (NF-κB) p65 subunit, the levels of activated (phosphorylated) c-jun N-terminal kinase (JNK) and cleaved caspase-3, and the secretion of TNF-α and IL-6 in B35 cells at 6 h after CoCl(2) treatment. These data suggest that IRAK-1/4 inhibition plays a neuroprotective role in H/I-induced brain injury. SN - 1873-7544 UR - https://www.unboundmedicine.com/medline/citation/21925238/Interleukin_1_receptor_associated_kinases_1/4_inhibition_protects_against_acute_hypoxia/ischemia_induced_neuronal_injury_in_vivo_and_in_vitro_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(11)01017-7 DB - PRIME DP - Unbound Medicine ER -