Effects of 15-lipoxygenase overexpressing adipose tissue mesenchymal stem cells on the Th17 / Treg plasticity

Autor: Alper Tunga Özdemir, Ayşe Nalbantsoy, Rabia Bilge Özgül Özdemir, Afig Berdeli
Rok vydání: 2022
Předmět:
green fluorescent protein
peripheral blood mononuclear cell
transcription factor T bet
Physiology
immunomodulation
T-Lymphocytes
Regulatory
Biochemistry
immune response
regulatory T lymphocyte
Transforming Growth Factor beta
mononuclear cell
transcription factor GATA 3
Arachidonate 15-Lipoxygenase
gene mutation
mesenchymal stem cell
Th17 cell
interleukin 17 antibody
cell plasticity
Interleukin-17
Forkhead Transcription Factors
Promote
enzyme activity
Interleukin-10
Treg
RNA isolation
arachidonate 15 lipoxygenase
Adipose Tissue
real time polymerase chain reaction
forkhead transcription factor
Th17
gamma interferon
retinoic acid receptor alpha
coculture
15-Lipoxygenase
WST assay
tumor necrosis factor
gene overexpression
adipose-derived mesenchymal stem cell
Generation
transcription factor FOXP3
Prostaglandin-E2
interleukin 6
phytohemagglutinin
interleukin 4
Article
reverse transcription polymerase chain reaction
Humans
controlled study
human
protein expression
cell viability
Pharmacology
Regulatory T-Cells
CD4+ T lymphocyte
Interleukin-6
flow cytometry
human cell
Induce
Mesenchymal Stem Cells
Lipoxin A4
Cell Biology
enzyme linked immunosorbent assay
arachidonic acid metabolism
cell proliferation
Leukocytes
Mononuclear
Th17 Cells
genetic transfection
Stromal Cells
Resolution
interleukin 10
interleukin 17
metabolism
Autoimmune
Interleukin-17a
Zdroj: Prostaglandins & Other Lipid Mediators. 159:106610
ISSN: 1098-8823
DOI: 10.1016/j.prostaglandins.2021.106610
Popis: 15-lipoxygenase (15-LOX) is a critical enzyme that allows the direction of arachidonic acid metabolism to change from inflammation into the resolution. This study aims to reveal how the immunomodulation properties of mesenchymal stem cells (MSC) alter by the 15-LOX overexpression. For this purpose, peripheral blood mononuclear cells (PBMCs) isolated from seven healthy volunteers, and both MSCs and 15-LOX overexpressing MSCs (15-LOXMSCs) were co-cultured at different cell ratios (1/1, 1/5 and 1/10). Alterations of CD4+Tbet+, CD4+Gata3+, CD4+RoRC2+, and CD4+FoxP3+ lymphocyte frequencies were detected by flow cytometry, and IFN-?, IL-4, IL-6, IL-10, IL-17a, TGF-? and LXA4 levels of medium supernatants were measured by ELISA method. According to our findings, MSC and 15-LOXMSCs have a suppressive effect on PHA activated PBMCs. However, as the ratio of PBMCs increased, the effects of 15-LOXMSCs increased significantly, while the effects of MSCs decreased. The most notable effect of the 15-LOX modification was the significant reduction in IL-6, IL-10 and IL-17a expression and the accompanying increase in TGF-? and LXA4 levels. We also observed a similar situation between CD4+RoRC2+ and CD4+FoxP3+ cell frequencies. These data suggested that the effects of MSCs on the balance of Th17 / Treg could change by the 15-LOX overexpression, and this might be in favor of the Treg cells. © 2021
16-TIP-041
The Scientific Research Projects Commission of Ege University financially supported the project for this study, with the reference number 16-TIP-041 .
Databáze: OpenAIRE
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