Critical care medicine
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Critical care medicine · Feb 2014
Inhibiting the Toll-Like Receptor 4 Toll/Interleukin-1 Receptor Domain Protects Against Hepatic Warm Ischemia and Reperfusion Injury in Mice.
During Toll-like receptor 4 signaling, the Toll/interleukin-1 receptor domain is essential for interactions with downstream Toll/interleukin-1 receptor domain-containing adaptor proteins. The aim of this study is to investigate the role of the Toll/interleukin-1 receptor domain in the Toll-like receptor 4 signaling pathway during hepatic ischemia and reperfusion injury. ⋯ Toll/interleukin-1 receptor domain inhibition disrupts the interaction of Toll-like receptor 4 with its adaptor proteins, which abrogates downstream signaling pathways and prevents the activation of nuclear factor-κB and Jun N-terminal kinase/p38. This reduction in signaling consequently reduces hepatic inflammation, cell apoptosis, and hepatic damage. Toll/interleukin-1 receptor domain-targeted therapy thus represents a new approach to inhibit the intracellular Toll-like receptor 4 signaling pathway and reveals novel therapeutic target sites, which will facilitate the development of specific therapeutic agents.