|کد مقاله||کد نشریه||سال انتشار||مقاله انگلیسی||ترجمه فارسی||نسخه تمام متن|
|6450759||1416141||2017||12 صفحه PDF||سفارش دهید||دانلود رایگان|
Negative regulation of Toll-like receptor-4 (TLR4) is anticipated to control the pathogen-induced exaggerated immune response. However, effective TLR4 antagonists with scarce off-target effects are yet to be developed. To fill this void, we sought to design small peptide-inhibitors of the TLR4/MD2âLPS interaction. Here we report novel TLR4-antagonistic peptides (TAP), identified through phage display, endowed with the LPS-induced proinflammation inhibition, and confirmed in mice. TAPs-attributed TLR4-antagonism were initially evaluated through NF-ÎºB inhibition in HEK-blue hTLR4 and RAW264.7Â cells, and further reinforced by the downregulation of MAPKs (mitogen-activated protein kinases), NF-ÎºB, interleukin 6, and suppression of the oxidative-stress products and iNOS in macrophages and human peripheral blood mononuclear cells (hPBMCs). Among these, TAP2 specifically halted the TLR4, but not other TLRs signaling, which was further confirmed by the biophysical kinetic assay. Finally, TAP2 diminished LPS-elicited systemic cytokine response inÂ vivo, suggesting that TAPs, specifically TAP2, have the potential to treat TLR4-mediated immune ailments.
Journal: Biomaterials - Volume 126, May 2017, Pages 49-60