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The helminth product ES-62 protects against septic shock via Toll-like receptor 4-dependent autophagosomal degradation of the adaptor MyD88 (Retracted article. See vol. 12, pg. 804, 2011)

Puneet, P. and McGrath, M. A. and Tay, H. K. and Al-Riyami, L. and Rzepecka, J. and Moochhala, S. M. and Pervaiz, S. and Harnett, M. M. and Harnett, W. and Melendez, A. J. (2011) The helminth product ES-62 protects against septic shock via Toll-like receptor 4-dependent autophagosomal degradation of the adaptor MyD88 (Retracted article. See vol. 12, pg. 804, 2011). Nature Immunology, 12. pp. 344-351. ISSN 1529-2908

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Abstract

Sepsis is one of the most challenging health problems worldwide. Here we found that phagocytes from patients with sepsis had considerable upregulation of Toll-like receptor 4 (TLR4) and TLR2; however, shock-inducing inflammatory responses mediated by these TLRs were inhibited by ES-62, an immunomodulator secreted by the filarial nematode Acanthocheilonema viteae. ES-62 subverted TLR4 signaling to block TLR2- and TLR4-driven inflammatory responses via autophagosome-mediated downregulation of the TLR adaptor-transducer MyD88. In vivo, ES-62 protected mice against endotoxic and polymicrobial septic shock by TLR4-mediated induction of autophagy and was protective even when administered after the induction of sepsis. Given that the treatments for septic shock at present are inadequate, the autophagy-dependent mechanism of action by ES-62 might form the basis for urgently needed therapeutic intervention against this life-threatening condition.

Item type: Article
ID code: 40582
Keywords: innate immunity, signal-transduction, cytokine production, intensive-care units, endotoxin, severe sepsis, responses, secreted product, epidemiology, definitions, helminth product , ES-62 , septic shock, protection, toll-like receptor , autophagosomal degradation , adaptor MyD88, Pharmacy and materia medica, Immunology
Subjects: Medicine > Pharmacy and materia medica
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
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Depositing user: Pure Administrator
Date Deposited: 26 Jul 2012 13:58
Last modified: 08 Aug 2014 05:12
URI: http://strathprints.strath.ac.uk/id/eprint/40582

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