Immunomodulatory effects of cyanobacterial toxincylindrospermopsin on innate immune cells
2019
Cylindrospermopsin (CYN), a cyanobacterial toxin, is an
important water pollutant with broad biological activity. It
has been known mainly from tropical areas, but the area of
occurrence of its producers is spreading to temperate climates.
It can be found in high concentrations in the environment as
well as in purified drinking waters. The aim of the study is to
bring a basic information on the ability of CYN to interfere
with mammalian innate immunity cells and thus increase the
understanding of the immunomodulatory potency of CYN. This
study investigated whether immune cells can be a target of CYN
either alone or in combination with a model immunomodulatory
agent, lipopolysaccharide (LPS). We examined the effects on
cellular viability and inflammation signaling of CYN on murine
macrophage-like RAW 264.7 cells. Macrophages were treated
either with pure toxin (1 mu M) or together with a known
stimulator of immunologically active cells, bacterial or
cyanobacterial LPS. CYN has had a significant effect on
production on pro-inflammatory mediator tumor necrosis factor
alpha (TNF-alpha) which correlates with its effect on reactive
oxygen species (ROS) production. We found that CYN potentiated
the effect of bacterial and cyanobacterial LPS that was
documented by activation of inflammatory signaling pathways
including mitogen-activated protein kinase p38 as well as
consequent expression of inducible nitric oxide synthase (iNOS)
and increased production of pro-inflammatory mediators such as
nitric oxide (NO), TNF-alpha, interleukin-6 (IL-6). Our study
brings one of the first information that contributes to the
elucidation of immunomodulatory role of CYN in macrophages
under normal and pro-inflammatory conditions.
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