A 12-mer Peptide of Tag7 (PGLYRP1) Forms a Cytotoxic Complex with Hsp70 and Inhibits TNF-Alpha Induced Cell Death

Cells. 2020 Feb 20;9(2):488. doi: 10.3390/cells9020488.


Investigation of interactions between a pro-inflammatory cytokine tumor necrosis factor (TNFα) and its receptor is required for the development of new treatments for autoimmune diseases associated with the adverse effects of TNFα. Earlier, we demonstrated that the innate immunity protein Tag7 (PGRP-S, PGLYRP1) can interact with the TNFα receptor, TNFR1, and block the transduction of apoptotic signals through this receptor. A complex formed between the Tag7 protein and the major heat shock protein Hsp70 can activate TNFR1 receptor and induce tumor cell death via either apoptotic or necroptotic pathway. In this study, we show that a 12-mer peptide, designated 17.1, which was derived from the Tag7 protein, can be regarded as a novel TNFα inhibitor, also is able to form a cytotoxic complex with the heat shock protein Hsp70. This finding demonstrates a new role for Hsp70 protein in the immune response. Also, this new inhibitory 17.1 peptide demonstrates an anti-inflammatory activity in the complete Freund's adjuvant (CFA)-induced autoimmune arthritis model in laboratory mice. It appears that the 17.1 peptide could potentially be used as an anti-inflammatory agent.

Keywords: Hsp70; TNFR1; Tag7; apoptosis; necroptosis; peptides; rheumatoid arthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / metabolism*
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use
  • Apoptosis / drug effects*
  • Arthritis, Rheumatoid / chemically induced
  • Arthritis, Rheumatoid / drug therapy
  • Cytokines / chemistry*
  • Cytokines / immunology
  • Disease Models, Animal
  • Female
  • Fibroblasts / metabolism
  • Freund's Adjuvant / adverse effects
  • HEK293 Cells
  • HSP70 Heat-Shock Proteins / metabolism*
  • Humans
  • Immunity, Innate
  • Mice
  • Mice, Inbred ICR
  • Necroptosis / drug effects
  • Peptides / metabolism*
  • Peptides / pharmacology*
  • Peptides / therapeutic use
  • Protein Binding
  • Receptors, Tumor Necrosis Factor, Type I / metabolism
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / immunology
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / metabolism


  • Anti-Inflammatory Agents
  • Cytokines
  • HSP70 Heat-Shock Proteins
  • PGLYRP1 protein, human
  • Peptides
  • Receptors, Tumor Necrosis Factor, Type I
  • Recombinant Proteins
  • TNFRSF1A protein, human
  • Tnfrsf1a protein, mouse
  • Tumor Necrosis Factor-alpha
  • Freund's Adjuvant