Blocking TIR Domain Interactions in TLR9 Signaling.

ABSTRACT: Interaction of TLR9 with ligands activates NF-κB, leading to proinflammatory cytokine production. Excessive TLR activation is a pathogenic factor for inflammatory diseases. This study has examined cell-permeating decoy peptides (CPDPs) derived from the TLR9 Toll/IL-1R resistance (TIR) domain. CPDP 9R34, which included AB loop, β-strand B, and N-terminal BB loop residues, inhibited TLR9 signaling most potently. CPDPs derived from α-helices C, D, and E (i.e., 9R6, 9R9, and 9R11) also inhibited TLR9-induced cytokines but were less potent than 9R34. 9R34 did not inhibit TLR2/1, TLR4, or TLR7 signaling. The N-terminal deletion modification of 9R34, 9R34-ΔN, inhibited TLR9 as potently as the full length 9R34. Binding of 9R34-ΔN to TIR domains was studied using cell-based Förster resonance energy

SUBMITTER: Javmen A 

PROVIDER: S-EPMC6057823 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature