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

International Journal of Molecular Sciences

Ekaterina Mironova¹  Svetlana Trofimova¹  Vladimir Kh. Khavinson¹  Antonio Domenico Procopio²  Giulia Giambuzzi³  Elena Toniato³  Stefano Martinotti³  Francesco Avolio³  Riccardo Pulcini³  Jessica Elisabetta Esposito³  Antonio Marino³  Pasquale Simeone⁴  Giuseppina Bologna⁴  Paola Lanuti⁴  Simone Guarnieri⁵  Iole Robuffo⁶ 

[1] Department of Biogerontology, Saint Petersburg Institute of Bioregulation and Gerontology, 197110 Saint Petersburg, Russia;Department of Clinical and Molecular Sciences, Politecnic University of Marche, 60121 Ancona, Italy;Department of Innovative Technology in Medicine and Odontoiatrics, Center of Advanced Studies and Technology University “G. d’Annunzio”, Chieti-Pescara, 66100 Chieti, Italy;Department of Medicine and Aging Sciences, Center of Advanced Studies and Technology University “G. d’Annunzio”, Chieti-Pescara, 66100 Chieti, Italy;Department of Neuroscience, Center of Advanced Studies and Technology, Imaging and Clinical Sciences, University of Chieti, 66100 Chieti, Italy;Institute of Molecular Genetics, National Research Council, Section of Chieti, 66100 Chieti, Italy;

关键词: peptides;    LPS;    monocytes;    cytokines;    STATs;   

DOI  :  10.3390/ijms23073607

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown