Macrophages morphology and cytokine reeducation by ex situ copper thiol complexes

Abstract

Objective

To study the reeducation effect of copper thiol complexes on macrophage morphology and cytokine expression.

Methods

The effect of copper thiol complexes was assessed on murine macrophages by the cell morphology observed through optical microscopy, while the expression of cytokines by protein abundance after stimulation. A viability experiment was performed on PMBC to confirm that copper complexes do not affect other cells.

Results

The M1 shape was reported after treatment with copper thiol complexes at 1–200 µM, while M2 behavior was documented between 50 and 800 µM. Surprisingly, a thin elongate morphology was observed between 400-800 µM like the M2 shape. The expression of M1 cytokines was noted ranging from 1 to 100 µM, with the highest yield at 1 µM (2243 pg/µL) for the copper-penicillamine complex. M2 production behavior was observed at 1–800 µM, with the highest abundance close to 1150 pg/µL (200–400 µM) was quantified from the copper-cysteine complex. Finally, LCCu complexes did not induce a cytotoxic response on PBMC while exhibiting a high IL-4 and IL-10 production, similar to their gold analogs.

Conclusions

The capacity of copper thiol complexes to reeducate M1 to M2 morphoexpression can be promising for cell protection by using copper thiol penicillamine or immuno-regeneration of tissues when using copper thiol cysteine.

Keywords:

• Reeducation
• copper thiol complexes
• macrophages
• morphology
• cytokine expression

Authors’ contribution

JX-T performed the experiments, cell morphology by ex situ cytokines, and in vitro assays with different copper thiol complexes concentrations; VEA-A participated in the conception and design of in vitro experiments, data analysis, writing, and review of the paper; FV-T participated in the design of cell biology management, analysis, interpretation, and critical revision; IC-Z participated in the implementation of the ELISA protocol and management of laboratory animals; RFV-C participated in the experimental work; JVC-R participated in idea generation, funding, writing the manuscript and coordinated the team.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by Consejo Nacional de Ciencia y Tecnología projects 1360 (Fronteras de la Ciencia) and 248378 (Atención a Problemas Nacionales).