tetano
Editor, Senior Moderator
Cell Rep. 2015 Jun 17. pii: S2211-1247(15)00571-9. doi: 10.1016/j.celrep.2015.05.035. [Epub ahead of print]
[h=1]A Decoy Peptide that Disrupts TIRAP Recruitment to TLRs Is Protective in a Murine Model of Influenza.[/h] Piao W[SUP]1[/SUP], Shirey KA[SUP]1[/SUP], Ru LW[SUP]1[/SUP], Lai W[SUP]1[/SUP], Szmacinski H[SUP]2[/SUP], Snyder GA[SUP]3[/SUP], Sundberg EJ[SUP]4[/SUP], Lakowicz JR[SUP]2[/SUP], Vogel SN[SUP]1[/SUP], Toshchakov VY[SUP]5[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Toll-like receptors (TLRs) activate distinct, yet overlapping sets of signaling molecules, leading to inflammatory responses to pathogens. Toll/interleukin-1 receptor (TIR) domains, present in all TLRs and TLR adapters, mediate protein interactions downstream of activated TLRs. A peptide library derived from TLR2 TIR was screened for inhibition of TLR2 signaling. Cell-permeable peptides derived from the D helix and the segment immediately N-terminal to the TLR2 TIR domain potently inhibited TLR2-mediated cytokine production. The D-helix peptide, 2R9, also potently inhibited TLR4, TLR7, and TLR9, but not TLR3 or TNF-α signaling. Cell imaging, co-immunoprecipitation, and in vitro studies demonstrated that 2R9 preferentially targets TIRAP. 2R9 diminished systemic cytokine responses elicited in vivo by synthetic TLR2 and TLR7 agonists; it inhibited the activation of macrophages infected with influenza strain A/PR/8/34 (PR8) and significantly improved the survival of PR8-infected mice. Thus, 2R9 represents a TLR-targeting agent that blocks protein interactions downstream of activated TLRs.
Copyright ? 2015 The Authors. Published by Elsevier Inc. All rights reserved.
PMID: 26095366 [PubMed - as supplied by publisher]
[h=1]A Decoy Peptide that Disrupts TIRAP Recruitment to TLRs Is Protective in a Murine Model of Influenza.[/h] Piao W[SUP]1[/SUP], Shirey KA[SUP]1[/SUP], Ru LW[SUP]1[/SUP], Lai W[SUP]1[/SUP], Szmacinski H[SUP]2[/SUP], Snyder GA[SUP]3[/SUP], Sundberg EJ[SUP]4[/SUP], Lakowicz JR[SUP]2[/SUP], Vogel SN[SUP]1[/SUP], Toshchakov VY[SUP]5[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Toll-like receptors (TLRs) activate distinct, yet overlapping sets of signaling molecules, leading to inflammatory responses to pathogens. Toll/interleukin-1 receptor (TIR) domains, present in all TLRs and TLR adapters, mediate protein interactions downstream of activated TLRs. A peptide library derived from TLR2 TIR was screened for inhibition of TLR2 signaling. Cell-permeable peptides derived from the D helix and the segment immediately N-terminal to the TLR2 TIR domain potently inhibited TLR2-mediated cytokine production. The D-helix peptide, 2R9, also potently inhibited TLR4, TLR7, and TLR9, but not TLR3 or TNF-α signaling. Cell imaging, co-immunoprecipitation, and in vitro studies demonstrated that 2R9 preferentially targets TIRAP. 2R9 diminished systemic cytokine responses elicited in vivo by synthetic TLR2 and TLR7 agonists; it inhibited the activation of macrophages infected with influenza strain A/PR/8/34 (PR8) and significantly improved the survival of PR8-infected mice. Thus, 2R9 represents a TLR-targeting agent that blocks protein interactions downstream of activated TLRs.
Copyright ? 2015 The Authors. Published by Elsevier Inc. All rights reserved.
PMID: 26095366 [PubMed - as supplied by publisher]