Peptides Regulating Proliferative Activity and Inflammatory Pathways in the Monocyte/Macrophage THP-1 Cell Line

Abstract

This study evaluates the effects of five different peptides, the Epitalon® tetrapeptide, the Vilon® dipeptide, the Thymogen® dipeptide, the Thymalin® peptide complex, and the Chonluten® tripeptide, as regulators of inflammatory and proliferative processes in the human monocytic THP-1, which is a human leukemia monocytic cell line capable of differentiating into macrophages by PMA in vitro. These peptides (Khavinson Peptides®), characterized by Prof. Khavinson from 1973 onwards, were initially isolated from animal tissues and found to be organ specific. We tested the capacity of the five peptides to influence cell cultures in vitro by incubating THP-1 cells with peptides at certain concentrations known for being effective on recipient cells in culture. We found that all five peptides can modulate key proliferative patterns, increasing tyrosine phosphorylation of mitogen-activated cytoplasmic kinases. In addition, the Chonluten tripeptide, derived from bronchial epithelial cells, inhibited in vitro tumor necrosis factor (TNF) production of monocytes exposed to pro-inflammatory bacterial lipopolysaccharide (LPS). The low TNF release by monocytes is linked to a documented mechanism of TNF tolerance, promoting attenuation of inflammatory action. Therefore, all peptides inhibited the expression of TNF and pro-inflammatory IL-6 cytokine stimulated by LPS on terminally differentiated THP-1 cells. Lastly, by incubating the THP1 cells, treated with the peptides, on a layer of activated endothelial cells (HUVECs activated by LPS), we observed a reduction in cell adhesion, a typical pro-inflammatory mechanism. Overall, the results suggest that the Khavinson Peptides® cooperate as natural inducers of TNF tolerance in monocyte, and act on macrophages as anti-inflammatory molecules during inflammatory and microbial-mediated activity.

The First Reciprocal Activities of Chiral Peptide Pharmaceuticals: Thymogen and Thymodepressin, as Examples

“…Our findings on such changes in the optical configuration of Glu-Trp isomers resulted in reciprocal changes in the magnitude and direction of their biological effects [3,66,67,70,71,77]. A significant difference between Tymodepressin and other drugs is its effect on activated cell clones without suppressing the activity of memory cells, i.e., without affecting previously acquired immunity.…”

“…As a result, pharmaceutical preparations, such as Thymogen and Thymodepressin, as well as stimulants and suppressors of the immune response, were introduced into clinical practice [77]. A new generation of the Glu-Trp peptide family derivatives as orally active peptidomimetics expresses the same type of activities as the first generation [107][108][109][110].…”

“…Experimental data and clinical results for Thymogen were presented in various publications and international conferences [65,76,77]. Experimental data on Thymogen are in the scope of published data for other peptide immunomodulators.…”

Anti-Obesity and Anti-Inflammatory Effects of Novel Carvacrol Derivatives on 3T3-L1 and WJ-MSCs Cells

“…To evaluate the anti-inflammatory effect of CD1-3 , THP-1 cells were used [ 41 ]. These cells derive from the peripheral blood of a childhood case of acute monocytic leukemia and are used as a model for human monocytes.…”

Advancement from Small Peptide Pharmaceuticals to Orally Active Piperazine-2,5-dion-Based Cyclopeptides

“…Therefore, Thymogen studies were conducted on animals exposed to ionizing radiation. Irradiation has a particularly destructive effect on lymphoid tissue, which is associated with its high radiosensitivity [26,27].…”