A 8-mer Peptide of PGLYRP1/Tag7 Innate Immunity Protein Binds to TNFR1 Receptor and Inhibits TNFα-Induced Cytotoxic Effect and Inflammation

Abstract

Search for novel regulatory protein fragments with potential functional roles is required both for understanding the immune response mechanisms and the development of targeted immunotherapy. Earlier we demonstrated that the PGLYRP1/Tag7 innate immunity protein can be regarded as an inhibitor of TNFα cytotoxic activity via the interaction with its TNF receptor 1 (TNFR1). A C-terminal peptide fragment 17.1 of the molecule is responsible for this function. In this study we have identified a minimal 8-mer region of this peptide (hereinafter – 17.1A) capable to bind to TNFR1. As a result of such interaction, the cytotoxic signals induced by this receptor are blocked. Also, this peptide demonstrates an anti-inflammatory activity in vivo in the complete Freund’s adjuvant (CFA)-induced arthritis model in laboratory mice. Peptide 17.1A is capable to reduce periarticular inflammation, inhibit the development of synovitis and exhibit a protective effect on cartilage and bone tissues. This peptide can turn out to be a promising medicinal agent for autoimmune arthritis and other diseases.

N-Terminal Peptide of PGLYRP1/Tag7 Is a Novel Ligand for TREM-1 Receptor

“…N9 is a part of the N3 peptide and is a sufficient motif to bind TREM-1. We have demonstrated in our previous works that the N-terminal peptide of Tag7 named N1 can bind to the TREM-1 receptor and decrease inflammation induced by LPS in PBMCs and mice [ 35 ]. Here, we have obtained the shortest peptide of N3 (N9) that is responsible for binding the TREM-1 receptor and does not reveal signal transduction.…”

“…C-terminal peptides of Tag7 called 17.1 and 17.1A interact with TNFR-1, and the N-terminal peptide of Tag7, named N1, binds to the TREM-1 receptor. These peptides blocked signaling pathways from these receptors and reduced inflammation in both in vivo and in vitro experiments [ 34 , 35 , 36 ].…”

Transcriptional sequencing analysis reveals the potential use of deer antler for “tonifying the kidney and strengthening bone”

“…MPO is a heme peroxidase, which plays a protective role in bone turnover by limiting osteoclastogenesis and bone resorption physiologically by modulating the intracellular H 2 O 2 concentration [ 33 ]. Peptide 17.1A is capable of reducing periarticular inflammation, inhibiting the development of synovitis, and exhibiting a protective effect on cartilage and bone tissues [ 34 ]. Lcp1 is a calcium-binding protein that regulates intracellular calcium by storing and releasing Ca 2+ , it coordinate the regulation of intracellular Ca 2+ during osteoblast differentiation [ 35 ].…”

Protein PGLYRP1/Tag7 Peptides Decrease the Proinflammatory Response in Human Blood Cells and Mouse Model of Diffuse Alveolar Damage of Lung through Blockage of the TREM-1 and TNFR1 Receptors

“…Both peptides inhibited TNFα-mediated cell death and slowed the progression of CFA-induced autoimmune arthritis. The preliminary results suggest that the TREM-1 binding region is located in the N-terminal of the Tag7 molecule [16,17]. An assumption can be made that these Tag7 fragments might be involved in the inflammatory response regulation.…”