Journal article

Publication year: 2021

Pages: 261-272

Journal: Journal of Molecular Medicine

Volume number: 99

Issue number: 2

ISSN: 0946-2716

eISSN: 1432-1440

Open access status: Hybrid

DOI Link: https://doi.org/10.1007/s00109-020-02024-4

Publisher: Springer

Abstract: 
Developing resistance mechanisms of pathogens against established and frequently used drugs are a growing global health problem. Besides the development of novel drug candidates per se, new approaches to counteract resistance mechanisms are needed. Drug candidates that not only target the pathogens directly but also modify the host immune system might boost anti-parasitic defence and facilitate clearance of pathogens. In this study, we investigated whether the novel anti-parasitic steroid compound 1o (sc1o), effective against the parasites Plasmodium falciparum and Schistosoma mansoni, might exhibit immunomodulatory properties. Our results reveal that 50 mu M sc1o amplified the inflammatory potential of M1 macrophages and shifted M2 macrophages in a pro-inflammatory direction. Since M1 macrophages used predominantly glycolysis as an energy source, it is noteworthy that sc1o increased glycolysis and decreased oxidative phosphorylation in M2 macrophages. The effect of sc1o on the differentiation and activation of dendritic cells was ambiguous, since both pro- and anti-inflammatory markers were regulated. In conclusion, sc1o has several immunomodulatory effects that could possibly assist the immune system by counteracting the anti-inflammatory immune escape strategy of the parasite P. falciparum or by increasing pro-inflammatory mechanisms against pathogens, albeit at a higher concentration than that required for the anti-parasitic effect. Key messages center dot The anti-parasitic steroid compound 1o (sc1o) can modulate human immune cells. center dot Sc1o amplified the potential of M1 macrophages. center dot Sc1o shifts M2 macrophages to a M1 phenotype. center dot Dendritic cell differentiation and activation was ambiguously modulated. center dot Administration of sc1o could possibly assist the anti-parasitic defence.

Harvard Citation style: Blum, L., Ulshöfer, T., Henke, M., Krieg, R., Berneburg, I., Geisslinger, G., et al. (2021) The immunomodulatory potential of the arylmethylaminosteroid sc1o, Journal of Molecular Medicine, 99(2), pp. 261-272. https://doi.org/10.1007/s00109-020-02024-4

APA Citation style: Blum, L., Ulshöfer, T., Henke, M., Krieg, R., Berneburg, I., Geisslinger, G., Becker, K., Parnham, M., & Schiffmann, S. (2021). The immunomodulatory potential of the arylmethylaminosteroid sc1o. Journal of Molecular Medicine. 99(2), 261-272. https://doi.org/10.1007/s00109-020-02024-4