Induced overexpression of MARCH-1 in human macrophages altered to M2 phenotype for suppressing inflammation process

The M1 macrophage is characterized by enhanced pro-inflammatory cytokines production, whereas macrophage (M2) has anti-inflammatory features. Macrophage polarization as a therapeutic target for controlling immune responses could be performed by gene transduction to control the regulation of exaggera...

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Bibliographic Details
Published in:Iranian journal of basic medical sciences 2022-04, Vol.25 (4), p.474-482
Main Authors: Zangeneh, Zivar, Khamisipour, Gholamreza, Andalib, Ali Reza
Format: Article
Language:English
Subjects:
Antigens
Chemokines
Cytokines
Dendritic cells
Enzymes
Genetic engineering
Genotype & phenotype
Immunology
Inflammation
inos
Lymphocytes
macrophage
march-1
Original
Plasmids
polarization
Proteins
tgf-beta
Viruses
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Summary:The M1 macrophage is characterized by enhanced pro-inflammatory cytokines production, whereas macrophage (M2) has anti-inflammatory features. Macrophage polarization as a therapeutic target for controlling immune responses could be performed by gene transduction to control the regulation of exaggerated innate/adaptive immune responses. Macrophages were prepared from THP-1 cell line and human monocytes that were transduced with (Membrane-Associated RING-CH-type finger) MARCH-1 viral lentivector produced in HEK-293T cells. RT-PCR and Western blotting confirmed MARCH-1 gene transduction. Cytokine production, CD markers assay, macrophage phagocytosis potential activity and mixed leukocyte reaction (MLR) with CFSE were performed for M1/M2 plasticity. The mean fluorescent intensity of HLA-DR and CD64 expression reduced in MARCH-1+ transduced macrophage population. However, CD206 and CD163 expression increased in these macrophages. The concentrations of IL-6, TNF-α and iNOS were decreased in MARCH-1 transduced cells, and TGF-β production showed an augmentation in concentration. Western blotting and real-time PCR measurement confirmed that the expression levels of MARCH-1 protein and arginase-1 enzyme were increased in transduced macrophages. The anti-inflammatory features of MARCH-1 revealed the reduced levels of pro-inflammatory factors and maintained M2 phenotype characterized by high levels of scavenger receptors. Therefore, targeting MARCH-1 in monocytes/macrophages could represent a new autologous cell-based therapies strategy for inflammatory conditions.
ISSN:2008-3866
2008-3874
DOI:10.22038/IJBMS.2022.62893.13902