Synthetic peptides containing ITIM-like sequences of IREM-1 (CD300F) differentially regulate MyD88 and TRIF-mediated TLR signalling through activation of SHP and/or PI3K

摘要: The immune receptor expressed on myeloid cells 1 (IREM-1/CD300F) has been shown to inhibit various inflammatory processes in cells, such as macrophages and mast cells. IREM-1 exerts its inhibitory effect through intracellular immunoreceptor tyrosine-based inhibition motifs (ITIMs). In order generate immunomodulatory molecules that can regulate the activation of macrophages, decapeptides representing each five ITIM-like sequences cytoplasmic tail were synthesized conjugation with human immunodeficiency virus-transactivator transcription (HIV-TAT48–57), which was added promote internalization peptides. Interestingly, all these TAT–ITIM fusion peptides inhibited Toll-like (TLR)-mediated production proinflammatory molecules, including matrix metalloproteinase (MMP)-9, tumour necrosis factor (TNF)-α, monocyte chemotactic protein-1 (MCP-1) interleukin (IL)-8. When TLR ligands used stimulate macrophage-like cell line acute monocytic leukaemia (THP)-1, blocked both differentiation 88 (MyD88) Toll-interleukin (TIR)-domain-containing adapter-inducing interferon-β (TRIF)-mediated signalling pathways. Utilization specific inhibitors detection active form adaptors by Western blot analysis further demonstrated effects require Src homology 2 (SH2)-containing tyrosine phosphatase (SHP) and/or phosphoinositide 3-kinase (PI3K). These data indicate synthetic may be responses involve TLR-mediated macrophages.