PMID- 31877847 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200928 IS - 2079-7737 (Print) IS - 2079-7737 (Electronic) IS - 2079-7737 (Linking) VI - 9 IP - 1 DP - 2019 Dec 22 TI - Modification of Tumor Necrosis Factor-alpha and C-C Motif Chemokine Ligand 18 Secretion by Monocytes Derived from Patients with Diabetic Foot Syndrome. LID - 10.3390/biology9010003 [doi] LID - 3 AB - Background: This study involves the investigation of spontaneous and induced secretion of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) 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. Methods: 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' blood and stimulated by interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) for induction of pro- and anti-inflammatory monocyte activation, respectively. The concentrations of TNF-alpha and CCL18 in the culture medium were measured using ELISA on day 1 and day 6 after cell stimulation. Results: We found a correlation between glycated hemoglobin (HbA1c) and stimulated secretion levels of TNF-alpha (r = 0.726, p = 0.027) and CCL18 (r = -0.949, p = 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 (p < 0.05). However, no stimulation of anti-inflammatory activation was detected in patients with DFS lasting more than 6 months (p = 0.033). Conclusions: 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. FAU - Galstyan, Karine O AU - Galstyan KO AD - Federal 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, Russia. AD - City Clinical Hospital numero sign 67 named after L.A. Vorokhobov, 123423 Moscow, Russia. FAU - Nedosugova, Ludmila V AU - Nedosugova LV AD - Federal 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, Russia. FAU - Martirosian, Narine S AU - Martirosian NS AUID- ORCID: 0000-0002-0202-1257 AD - Federal 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, Russia. AD - City Clinical Hospital numero sign 67 named after L.A. Vorokhobov, 123423 Moscow, Russia. FAU - Nikiforov, Nikita G AU - Nikiforov NG AD - Laboratory of Medical Genetics, Institute of Experimental Cardiology, National Medical Research Center of Cardiology, 121552 Moscow, Russia. AD - Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia. AD - Center of Collective Usage, Institute of Gene Biology, 119991 Moscow, Russia. FAU - Elizova, Natalia V AU - Elizova NV AD - Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia. FAU - Kolmychkova, Kira I AU - Kolmychkova KI AUID- ORCID: 0000-0002-2953-5901 AD - Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia. FAU - Sobenin, Igor A AU - Sobenin IA AUID- ORCID: 0000-0003-0978-6444 AD - Laboratory of Medical Genetics, Institute of Experimental Cardiology, National Medical Research Center of Cardiology, 121552 Moscow, Russia. AD - Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia. AD - Research Institute of Threpsology and Healthy Longevity, Plekhanov Russian University of Economics, 117997 Moscow, Russia. FAU - Orekhov, Alexander N AU - Orekhov AN AUID- ORCID: 0000-0002-3318-4681 AD - Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia. LA - eng GR - 19-15-00010/Russian Science Foundation/ PT - Journal Article DEP - 20191222 PL - Switzerland TA - Biology (Basel) JT - Biology JID - 101587988 PMC - PMC7168305 OTO - NOTNLM OT - C-C motif chemokine ligand 18 OT - anti-inflammatory OT - chemokine OT - cytokine OT - diabetic foot syndrome OT - monocyte response OT - pro-inflammatory OT - tumor necrosis factor-alpha OT - type 2 diabetes mellitus COIS- The authors declare no conflict of interest. EDAT- 2019/12/28 06:00 MHDA- 2019/12/28 06:01 PMCR- 2020/01/01 CRDT- 2019/12/28 06:00 PHST- 2019/11/18 00:00 [received] PHST- 2019/12/18 00:00 [revised] PHST- 2019/12/19 00:00 [accepted] PHST- 2019/12/28 06:00 [entrez] PHST- 2019/12/28 06:00 [pubmed] PHST- 2019/12/28 06:01 [medline] PHST- 2020/01/01 00:00 [pmc-release] AID - biology9010003 [pii] AID - biology-09-00003 [pii] AID - 10.3390/biology9010003 [doi] PST - epublish SO - Biology (Basel). 2019 Dec 22;9(1):3. doi: 10.3390/biology9010003.