Immunomodulatory Potency of Microcystin, an Important Water-Polluting Cyanobacterial Toxin

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Authors

ADAMOVSKÝ Ondřej MOOSOVÁ Zdena PEKAROVA Michaela BASU Amrita BABICA Pavel SINDLEROVA Lenka Svihalkova KUBALA Lukáš BLÁHA Luděk

Year of publication 2015
Type Article in Periodical
Magazine / Source Environmental Science and Technology
MU Faculty or unit

Faculty of Science

Citation
Web http://pubs.acs.org/doi/10.1021/acs.est.5b02049
Doi http://dx.doi.org/10.1021/acs.est.5b02049
Field Water pollution and control
Keywords NF-KAPPA-B; NECROSIS-FACTOR-ALPHA; TOLL-LIKE RECEPTORS; ANION TRANSPORTING POLYPEPTIDES; ACTIVATED PROTEIN-KINASE; MELANOMA-CELL INVASION; LIVER-TUMOR PROMOTION; NITRIC-OXIDE; SIGNALING PATHWAYS; IN-VITRO
Description Microcystins (MCs) are primarily hepatotoxins produced by cyanobacteria and are responsible for intoxication in humans and animals. There are many incidents of chronic exposure to MCs, which have been attributed to the inappropriate treatment of water supplies or contaminated food. Using RAW 264.7 macrophages, we showed the potency of microcystin-LR (MC-LR) to stimulate production of pro-inflammatory cytokines (tumor necrosis factor alpha and interleukin-6) as a consequence of fast nuclear factor kappa B and nitrogen-activated protein kinase activation. In contrast to other studies, the observed effects were not attributed to the intracellular inhibition of protein phosphatases 1/2A due to lack of specific transmembrane transporters for MCs. However, the MC-LR-induced activation of macrophages was effectively inhibited by a specific peptide that blocks signaling of receptors, which play a pivotal role in the innate immune responses. Taken together, we showed for the first time that MC-LR could interfere with macrophage receptors that are responsible for triggering the above-mentioned signaling pathways. These findings provide an interesting mechanistic explanation of some adverse health outcomes associated with toxic cyanobacteria and MCs.
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