title: Immunomodulatory Potency of Microcystin, an Important Water-Polluting Cyanobacterial Toxin.
abstract: 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 α and interleukin-6) as a consequence of fast nuclear factor κB 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.
authors.affiliation: Faculty of Science, RECETOX, Masaryk University , Kamenice 753/5, 62500 Brno, Czech Republic.
authors.forename: Ondrej
authors.initials: O
authors.lastname: Adamovsky
authors.affiliation: Faculty of Science, RECETOX, Masaryk University , Kamenice 753/5, 62500 Brno, Czech Republic.
authors.forename: Zdena
authors.initials: Z
authors.lastname: Moosova
authors.affiliation: Institute of Biophysics, Academy of Sciences , Královopolská 135, 612 65 Brno, Czech Republic.
authors.forename: Michaela
authors.initials: M
authors.lastname: Pekarova
authors.affiliation: Faculty of Science, RECETOX, Masaryk University , Kamenice 753/5, 62500 Brno, Czech Republic.
authors.forename: Amrita
authors.initials: A
authors.lastname: Basu
authors.affiliation: Faculty of Science, RECETOX, Masaryk University , Kamenice 753/5, 62500 Brno, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Babica
authors.affiliation: Institute of Biophysics, Academy of Sciences , Královopolská 135, 612 65 Brno, Czech Republic.
authors.forename: Lenka
authors.initials: L
authors.lastname: Svihalkova Sindlerova
authors.affiliation: Institute of Biophysics, Academy of Sciences , Královopolská 135, 612 65 Brno, Czech Republic.
authors.forename: Lukas
authors.initials: L
authors.lastname: Kubala
authors.affiliation: Faculty of Science, RECETOX, Masaryk University , Kamenice 753/5, 62500 Brno, Czech Republic.
authors.forename: Ludek
authors.initials: L
authors.lastname: Blaha
mesh_terms: D000818:Animals; D002460:Cell Line / Q000187:drug effects; D000458:Cyanobacteria / Q000472:pathogenicity*; D007113:Immunity, Innate / Q000187:drug effects*; D007155:Immunologic Factors / Q000633:toxicity; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008387:Marine Toxins; D051379:Mice; D052998:Microcystins / Q000633:toxicity*; D016328:NF-kappa B / Q000378:metabolism; D054648:Protein Phosphatase 2 / Q000378:metabolism; D036401:Toxicity Tests, Chronic / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D014881:Water Supply
chemical_list: D007155:Immunologic Factors; D015850:Interleukin-6; D008387:Marine Toxins; D052998:Microcystins; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D014874:Water Pollutants, Chemical; C577686:interleukin-6, mouse; D054648:Protein Phosphatase 2; C057862:cyanoginosin LR