A 12-mer Peptide of Tag7 (PGLYRP1) Forms a Cytotoxic Complex with Hsp70 and Inhibits TNF-Alpha Induced Cell Death
Elena A. Romanova,
Tatiana N. Sharapova,
Georgii B. Telegin,
Alexei N. Minakov,
Alexander S. Chernov,
Olga K. Ivanova,
Maxim L. Bychkov,
Lidia P. Sashchenko,
Denis V. Yashin
Affiliations
Elena A. Romanova
Laboratory of Molecular immunogenetics of cancer, Institute of gene biology RAS, Vavilova 34/5, 111394 Moscow, Russia
Tatiana N. Sharapova
Laboratory of Molecular immunogenetics of cancer, Institute of gene biology RAS, Vavilova 34/5, 111394 Moscow, Russia
Georgii B. Telegin
Branch of Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Prospect Nauki 6, 142290 Pushchino, Russia
Alexei N. Minakov
Branch of Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Prospect Nauki 6, 142290 Pushchino, Russia
Alexander S. Chernov
Branch of Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Prospect Nauki 6, 142290 Pushchino, Russia
Olga K. Ivanova
Laboratory of Molecular immunogenetics of cancer, Institute of gene biology RAS, Vavilova 34/5, 111394 Moscow, Russia
Maxim L. Bychkov
Laboratory of bioengineering of neuromodulators and neuroreceptors, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Miklucho-Maklaya str., 16/10, 117997 Moscow, Russia
Lidia P. Sashchenko
Laboratory of Molecular immunogenetics of cancer, Institute of gene biology RAS, Vavilova 34/5, 111394 Moscow, Russia
Denis V. Yashin
Laboratory of Molecular immunogenetics of cancer, Institute of gene biology RAS, Vavilova 34/5, 111394 Moscow, Russia
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.
