Evaluation of THP-1 and Jurkat Cell Lines Coculture for the In Vitro Assessment of the Effects of Immunosuppressive Substances

The strong appeal to reduce animal testing calls for the development and validation of in vitro, in chemico and in silico models that would replace the need for in vivo testing and ex vivo materials. A category that requires such new approach methods is the assessment of immunosuppression that can b...

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Bibliographic Details
Published in:Toxics (Basel) 2024-08, Vol.12 (8), p.607
Main Authors: Franko, Nina, Sollner Dolenc, Marija
Format: Article
Language:English
Subjects:
Animal models
Antigens
Autoimmune diseases
bisphenols
Blood & organ donations
Cell activation
Cell culture
Cell cycle
Cell lines
coculture
Cytokines
Drug delivery
Drug development
Experiments
Immune system
Immunosuppression
Immunosuppressive agents
in vitro
In vitro methods and tests
In vivo methods and tests
Lymphocytes
Metabolism
Monocytes
new approach method
Pollutants
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Summary:The strong appeal to reduce animal testing calls for the development and validation of in vitro, in chemico and in silico models that would replace the need for in vivo testing and ex vivo materials. A category that requires such new approach methods is the assessment of immunosuppression that can be induced by chemicals including environmental pollutants. To assess the immunosuppressive action on monocytes and lymphocytes, we mimicked the whole-blood cytokine-release assay by preparing an in vitro coculture of THP-1 and Jurkat cell lines. We optimised its activation and investigated the effects of known immunosuppressive drugs with different mechanisms of action on the release of proinflammatory cytokines. Decreased secretion of IL-8 was achieved by several immunosuppressive mechanisms and was therefore selected as an appropriate marker of immunosuppression. A set of environmentally occurring bisphenols, BPA, BPAP, BPP, BPZ, BPE, TCBPA and BPS-MAE, were then applied to the model and BPP and BPZ were found to act as potent immunosuppressants at micromolar concentrations.
ISSN:2305-6304
2305-6304
DOI:10.3390/toxics12080607