Modification of Tumor Necrosis Factor-α and C-C Motif Chemokine Ligand 18 Secretion by Monocytes Derived from Patients with Diabetic Foot Syndrome

<b>Background:</b> This study involves the investigation of spontaneous and induced secretion of the pro-inflammatory cytokine tumor necrosis factor-&#945; (TNF-&#945;) and the anti-inflammatory chemokine C-C motif chemokine ligand 18 (CCL18) by monocytes isolated from blood of p...

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Main Authors: Karine O. Galstyan, Ludmila V. Nedosugova, Narine S. Martirosian, Nikita G. Nikiforov, Natalia V. Elizova, Kira I. Kolmychkova, Igor A. Sobenin, Alexander N. Orekhov
Format: Article
Language:English
Published: MDPI AG 2019-12-01
Series:Biology
Subjects:
Online Access:https://www.mdpi.com/2079-7737/9/1/3
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spelling doaj-9ac28234fb0a42179edf195a18b9e98f2020-11-25T02:22:01ZengMDPI AGBiology2079-77372019-12-0191310.3390/biology9010003biology9010003Modification of Tumor Necrosis Factor-α and C-C Motif Chemokine Ligand 18 Secretion by Monocytes Derived from Patients with Diabetic Foot SyndromeKarine O. Galstyan0Ludmila V. Nedosugova1Narine S. Martirosian2Nikita G. Nikiforov3Natalia V. Elizova4Kira I. Kolmychkova5Igor A. Sobenin6Alexander N. Orekhov7Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of the Russian Federation, 119991 Moscow, RussiaFederal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of the Russian Federation, 119991 Moscow, RussiaFederal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of the Russian Federation, 119991 Moscow, RussiaLaboratory of Medical Genetics, Institute of Experimental Cardiology, National Medical Research Center of Cardiology, 121552 Moscow, RussiaLaboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315 Moscow, RussiaLaboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315 Moscow, RussiaLaboratory of Medical Genetics, Institute of Experimental Cardiology, National Medical Research Center of Cardiology, 121552 Moscow, RussiaLaboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia<b>Background:</b> This study involves the investigation of spontaneous and induced secretion of the pro-inflammatory cytokine tumor necrosis factor-&#945; (TNF-&#945;) and the anti-inflammatory chemokine C-C motif chemokine ligand 18 (CCL18) by monocytes isolated from blood of patients with long-term type 2 diabetes mellitus (T2DM), both with or without foot ulcers. <b>Methods:</b> A total of 121 patients with T2DM (79 without diabetic foot syndrome (DFS) and 42 patients with DFS) were included. Cluster of Differentiation 14 (CD14+) monocytes were isolated from patients&#8217; blood and stimulated by interferon-&#947; (IFN-&#947;) and interleukin-4 (IL-4) for induction of pro- and anti-inflammatory monocyte activation, respectively. The concentrations of TNF-&#945; and CCL18 in the culture medium were measured using ELISA on day 1 and day 6 after cell stimulation. <b>Results:</b> We found a correlation between glycated hemoglobin (HbA1c) and stimulated secretion levels of TNF-&#945; (<i>r</i> = 0.726, <i>p</i> = 0.027) and CCL18 (<i>r</i> = &#8722;0.949, <i>p</i> = 0.051) in patients with DFS. There was an increase of pro- and anti-inflammatory activation of monocytes in all patients with different durations of DFS (<i>p</i> &lt; 0.05). However, no stimulation of anti-inflammatory activation was detected in patients with DFS lasting more than 6 months (<i>p</i> = 0.033). <b>Conclusions:</b> Our study showed an increase in pro-inflammatory secretion and a decrease in anti-inflammatory secretion by monocytes isolated from blood of patients with T2DM depending on HbA1c levels and duration of the inflammatory process. These findings allow us to assume that monocytes isolated from T2DM patients are characterized by a biased ability to respond towards pro-inflammatory stimulation, contributing to the chronic wound process.https://www.mdpi.com/2079-7737/9/1/3type 2 diabetes mellitusdiabetic foot syndromemonocyte responsepro-inflammatorycytokineanti-inflammatorychemokinetumor necrosis factor-αc-c motif chemokine ligand 18
collection DOAJ
language English
format Article
sources DOAJ
author Karine O. Galstyan
Ludmila V. Nedosugova
Narine S. Martirosian
Nikita G. Nikiforov
Natalia V. Elizova
Kira I. Kolmychkova
Igor A. Sobenin
Alexander N. Orekhov
spellingShingle Karine O. Galstyan
Ludmila V. Nedosugova
Narine S. Martirosian
Nikita G. Nikiforov
Natalia V. Elizova
Kira I. Kolmychkova
Igor A. Sobenin
Alexander N. Orekhov
Modification of Tumor Necrosis Factor-α and C-C Motif Chemokine Ligand 18 Secretion by Monocytes Derived from Patients with Diabetic Foot Syndrome
Biology
type 2 diabetes mellitus
diabetic foot syndrome
monocyte response
pro-inflammatory
cytokine
anti-inflammatory
chemokine
tumor necrosis factor-α
c-c motif chemokine ligand 18
author_facet Karine O. Galstyan
Ludmila V. Nedosugova
Narine S. Martirosian
Nikita G. Nikiforov
Natalia V. Elizova
Kira I. Kolmychkova
Igor A. Sobenin
Alexander N. Orekhov
author_sort Karine O. Galstyan
title Modification of Tumor Necrosis Factor-α and C-C Motif Chemokine Ligand 18 Secretion by Monocytes Derived from Patients with Diabetic Foot Syndrome
title_short Modification of Tumor Necrosis Factor-α and C-C Motif Chemokine Ligand 18 Secretion by Monocytes Derived from Patients with Diabetic Foot Syndrome
title_full Modification of Tumor Necrosis Factor-α and C-C Motif Chemokine Ligand 18 Secretion by Monocytes Derived from Patients with Diabetic Foot Syndrome
title_fullStr Modification of Tumor Necrosis Factor-α and C-C Motif Chemokine Ligand 18 Secretion by Monocytes Derived from Patients with Diabetic Foot Syndrome
title_full_unstemmed Modification of Tumor Necrosis Factor-α and C-C Motif Chemokine Ligand 18 Secretion by Monocytes Derived from Patients with Diabetic Foot Syndrome
title_sort modification of tumor necrosis factor-α and c-c motif chemokine ligand 18 secretion by monocytes derived from patients with diabetic foot syndrome
publisher MDPI AG
series Biology
issn 2079-7737
publishDate 2019-12-01
description <b>Background:</b> This study involves the investigation of spontaneous and induced secretion of the pro-inflammatory cytokine tumor necrosis factor-&#945; (TNF-&#945;) and the anti-inflammatory chemokine C-C motif chemokine ligand 18 (CCL18) by monocytes isolated from blood of patients with long-term type 2 diabetes mellitus (T2DM), both with or without foot ulcers. <b>Methods:</b> A total of 121 patients with T2DM (79 without diabetic foot syndrome (DFS) and 42 patients with DFS) were included. Cluster of Differentiation 14 (CD14+) monocytes were isolated from patients&#8217; blood and stimulated by interferon-&#947; (IFN-&#947;) and interleukin-4 (IL-4) for induction of pro- and anti-inflammatory monocyte activation, respectively. The concentrations of TNF-&#945; and CCL18 in the culture medium were measured using ELISA on day 1 and day 6 after cell stimulation. <b>Results:</b> We found a correlation between glycated hemoglobin (HbA1c) and stimulated secretion levels of TNF-&#945; (<i>r</i> = 0.726, <i>p</i> = 0.027) and CCL18 (<i>r</i> = &#8722;0.949, <i>p</i> = 0.051) in patients with DFS. There was an increase of pro- and anti-inflammatory activation of monocytes in all patients with different durations of DFS (<i>p</i> &lt; 0.05). However, no stimulation of anti-inflammatory activation was detected in patients with DFS lasting more than 6 months (<i>p</i> = 0.033). <b>Conclusions:</b> Our study showed an increase in pro-inflammatory secretion and a decrease in anti-inflammatory secretion by monocytes isolated from blood of patients with T2DM depending on HbA1c levels and duration of the inflammatory process. These findings allow us to assume that monocytes isolated from T2DM patients are characterized by a biased ability to respond towards pro-inflammatory stimulation, contributing to the chronic wound process.
topic type 2 diabetes mellitus
diabetic foot syndrome
monocyte response
pro-inflammatory
cytokine
anti-inflammatory
chemokine
tumor necrosis factor-α
c-c motif chemokine ligand 18
url https://www.mdpi.com/2079-7737/9/1/3
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