Immunomodulatory Effects of Cylindrospermopsin in Human T Cells and Monocytes

Toxins (Basel). 2023 Apr 20;15(4):301. doi: 10.3390/toxins15040301.

Abstract

Cylindrospermopsin (CYN) is a cyanotoxin with an increasing occurrence, and therefore it is important to elucidate its toxicity profile. CYN has been classified as a cytotoxin, although the scientific literature has already revealed that it affects a wide range of organs and systems. However, research on its potential immunotoxicity is still limited. Thus, this study aimed to evaluate the impact of CYN on two human cell lines representative of the immune system: THP-1 (monocytes) and Jurkat (lymphocytes). CYN reduced cell viability, leading to mean effective concentrations (EC50 24 h) of 6.00 ± 1.04 µM and 5.20 ± 1.20 µM for THP-1 and Jurkat cells, respectively, and induced cell death mainly by apoptosis in both experimental models. Moreover, CYN decreased the differentiation of monocytes to macrophages after 48 h of exposure. In addition, an up-regulation of the mRNA expression of different cytokines, such as interleukin (IL) 2, IL-8, tumor necrosis factor-alpha (TNF-α) and interferon-gamma (INF-γ), was also observed mainly after 24 h exposure in both cell lines. However, only an increase in TNF-α in THP-1 supernatants was observed by ELISA. Overall, these results suggest the immunomodulatory activity of CYN in vitro. Therefore, further research is required to evaluate the impact of CYN on the human immune system.

Keywords: Jurkat cells; THP-1 cells; cylindrospermopsin; immunotoxicity; in vitro toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Toxins* / toxicity
  • Humans
  • Monocytes
  • T-Lymphocytes
  • Tumor Necrosis Factor-alpha / genetics
  • Uracil / toxicity

Substances

  • cylindrospermopsin
  • Bacterial Toxins
  • Tumor Necrosis Factor-alpha
  • Uracil

Grants and funding

This research was funded by the Spanish Ministerio de Ciencia e Innovación, project number PID 2019-104890RB-I00/AEI/10.13039/501100011033. A.C.-R. acknowledges the Spanish Ministerio de Ciencia e Innovación for the predoctoral grant awarded, grant number PRE 2020-094412.