id author title date pages extension mime words sentences flesch summary cache txt cord-001385-rb5vwolt Reuven, Eliran Moshe The HIV-1 Envelope Transmembrane Domain Binds TLR2 through a Distinct Dimerization Motif and Inhibits TLR2-Mediated Responses 2014-08-14 .txt text/plain 6147 318 51 Figure 1A and B show that 20 minutes after addition of LTA to RAW cells that were pre-incubated with the gp41 TMD peptide, there was a significant decrease in ERK1,2 phosphorylation compared to nontreated cells, indicating less receptor activation. We next measured the expression levels of NFkB downstream genes; Tumor Necrosis Factor a (TNFa), a hallmark cytokine of TLR activation, and Monocyte Chemotactic Protein 1 (MCP-1), a major chemokine mainly secreted by macrophages [22] , in order to ensure that the inhibitive effect on ERK1,2 phosphorylation is a result of inhibition of TLR2 signaling. IL-6 is an additional target gene of TLR2 but it is transcribed via a different transcription factor complex than TNFa. Cells were pre-incubated with ENV TMD peptides for two hours prior to LTA activation. In order to confirm this hypothesis we utilized the ectopic expression of HIV-1 ENV-YFP chimeric protein in RAW 264.7 cells, which mimics the HIV-1 infection of macrophages, and tested their responsiveness to LTA by measuring TNFa secretion. ./cache/cord-001385-rb5vwolt.txt ./txt/cord-001385-rb5vwolt.txt