Iranian Journal of Basic Medical Sciences

Iranian Journal of Basic Medical Sciences

Alteration of immunoregulatory genes expression in mesenchymal stromal cells upon priming with B18R as an interferon binding protein

Document Type : Original Article

Authors
Hamid Reza Bidkhori 1
Moein Farshchian 2
Mahboubeh Kazemi Noughabi 3
Halimeh Hassanzadeh 2
Houshang RafatPanah 4
1 Immunology Research Center, Inflammation and Inflammatory Diseases Division, Mashhad University of Medical Sciences, Mashhad, Iran
2 Stem Cells and Regenerative Medicine Department, Academic Center for Education, Culture, and Research (ACECR)-Khorasan Razavi, Mashhad, Iran
3 Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran
4 Immunology Research Center, Inflammation and inflammatory Diseases Division, Mashhad University of Medical Sciences, Mashhad, Iran
10.22038/ijbms.2022.67353.14771
Abstract
Objective(s): The B18R protein encoded by the Vaccinia virus decoys Type 1 interferons and inhibits the activity of several type I IFN members. In vitro transcription protocols benefit from this molecule’s involvement in enhancing cell viability by inhibiting interferon signal transduction. As a result of their immunomodulatory properties and potential to regenerate, mesenchymal stromal cells (MSCs) are increasingly considered an alternative treatment for a wide range of immune disorders. In this study, we investigated the modification of expression of several genes involved in immune-related pathways after preconditioning MSCs with two immune stimuli, including poly(I:C) and LPS. 
Materials and Methods: ASCs were isolated and primed with B18R, and after exposure to poly(I:C) and LPS, the expression of the same sets of genes as in the previous experiment was evaluated. Following total RNA isolation from primed cells and cDNA preparation, real-time quantitative PCR was performed for several immunomodulatory and immune-related genes, including IDO1, TDO2, COX-2, TGF-β1, TNF-α, IL-1β, IL-6, TLR3, TLR4, and MCP-1. 
Results: Pretreatment of MSCs with poly(I:C) and LPS significantly increased the expression of all mentioned genes, while upon the B18R challenge followed by poly(I:C) and LPS treatment, they were down-regulated. Finally, it was observed that the relative expression level of IFN-β has significantly decreased in MSCs+B18R+poly(I:C) and LPS in comparison with these groups without B18R.
Conclusion: The data indicated that the presence of B18R prevents the overexpression of several immune-related genes, which are overexpressed in the in vitro inflammatory environment.
Keywords
B18R
Gene expression
Immune-related genes
Interleukin
lipopolysaccharide
Mesenchymal stromal cells
poly(I:C)
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Iranian Journal of Basic Medical Sciences
Volume 26, Issue 2
February 2023
Pages 241-247