Short Peptides of Innate Immunity Protein Tag7 Inhibit the Production of Cytokines in CFA-Induced Arthritis

Abstract

The pathogenesis of autoimmune arthritis is a hot topic in current research. The main focus of this work was to study cytokines released in CFA-induced arthritis in ICR mice as well as the regulation of blood levels of cytokines by two peptides of the innate immunity protein Tag7 (PGLYRP1) capable of blocking the activation of the TNFR1 receptor. Arthritis was induced by local periarticular single-dose injections of 40 µL of complete Freund’s adjuvant (CFA) into the left ankle joints of mice. The levels of chemokines and cytokines in plasma were measured using a Bio-Plex Pro Mouse Cytokine Kit at 3, 10, and 21 days after arthritis induction. Tag7 peptides were shown to decrease the blood levels of the pro-inflammatory cytokines IL-6, TNF, and IL-1β. Administration of peptides also decreased the levels of chemokines MGSA/CXCL1, MIP-2α/CXCL2, ENA78/CXCL5, MIG/CXCL9, IP-10/CXCL10, MCP-1/CCL2, and RANTES/CCL5. Furthermore, a decrease in the levels of cytokines IL7, G-CSF, and M-CSF was demonstrated. Addition of the studied peptides strongly affected IFN-γ concentration. We believe that a decrease in the levels of cytokine IFN-γ was associated with a therapeutic effect of Tag7 peptides manifested in alleviation of the destruction of cartilage and bone tissues in the CFA-induced arthritis.

The 12-Membered TNFR1 Peptide, as Well as the 16-Membered and 6-Membered TNF Peptides, Regulate TNFR1-Dependent Cytotoxic Activity of TNF

“…Shortened fragments of this peptide were also identified, responsible for only one function: inhibitory or cytotoxic [34]. Inhibitory peptides had a noticeable protective effect on the development of CFA-dependent autoimmune arthritis [40].…”

Short Peptides of Innate Immunity Protein Tag7 (PGLYRP1) Selectively Induce Inhibition or Activation of Tumor Cell Death via TNF Receptor

“…%) (15 mL of the mixture per g of peptidyl polymer) for 2 h. The solution was filtered; the untreated peptide was precipitated with a tenfold volume of diethyl ether and kept at a temperature of 4 • C for 8 h. The precipitated peptide was centrifuged, washed three times with diethyl ether and dried under vacuum. The untreated peptide was purified by HPLC on a YMC Actus Triart C18 10u 30 × 150 mm column in a gradient of 5-55% acetonitrile and lyophilized [32].…”

Research of Pathogenesis and Novel Therapeutics in Arthritis 3.0

“…Ostojic and colleagues suggest that it may be worth blocking macrophageal and leukocyte NF-κB expression to slow the disease behavior of OA [ 2 ]. The other research group indicates that cytokines released in complete Freund’s adjuvant (CFA)-induced arthritis in ICR mice as well as the regulation of blood levels of cytokines by two peptides of the innate immunity protein Tag7 (PGLYRP1) capable of blocking the activation of the TNFR1 receptor [ 3 ]. The Taiwanese research group also demonstrates that IL-17 promotes vascular cell adhesion molecule 1 (VCAM-1) production in human OA synovial fibroblasts (OASFs) and subsequently increases monocyte adhesion by reducing miR-5701 expression through the PKC-α and JNK signaling cascades, which may help with the design of more effective OA treatments [ 4 ].…”