Immunomodulatory effects of selected cyanobacterial peptides in vitro

Abstract

Cyanobacteria produce many biologically active metabolites synthesized via nonribosomal synthetic pathways such as cyclic microcystins (MCs) and linear aeruginosins (Aers). The present study aimed to investigate the effects of different MC variants and the newly isolated aerugenosin Aer-865 on macrophages, which represent one of the key effector cells within the innate immune responses. Specifically, our study included RAW 264.7 macrophage activation associated with production of cytotoxic and cytostatic nitric oxide (NO) as well as pro-inflammatory mediators like tumor necrosis factor α (TNFα) and interleukin 6 (IL-6). From the compounds investigated, commonly occurring MC variants (-RR, -YR) and Aer-865 had no significant effects within the non-cytotoxic concentrations tested, i.e. 0.001-1 μM for MCs and 0.1-50 μM for Aer-865. In contrast to known immunoactive MC-LR, the negligible immunomodulatory potential of tested MC congeners could be related to their differences in structure. The knowledge of MC structure-specific activities contributes to the understanding of complex toxicity of different MC variants and most importantly their mixtures. This study is one of the first study that evaluate the effect of larger set of cyanobacterial peptides on macrophages and compare their immunomodulatory potential.

Cyanobacteria Microcystis aeruginosa Contributes to the Severity of Fish Diseases: A Study on Spring Viraemia of Carp

“…Although previous studies show that both SVCV and cyanobacteria deregulate the immune system [6][7][8], we observed that the combination of stressors (B+SVC) has unique characteristics and impact on immunity. Specifically, in comparison to control and effects of individual stressors, solely combined exposure to B+SVC resulted in a dramatic rise in the production of immunoglobulins (Figure 2).…”

“…Although an individual stressor present in the environment may not represent a significant risk for aquatic organisms, a combination of multiple factors can produce unforeseen effects, especially if they target the same biological system or function (e.g., immune system). Despite the immunomodulatory potency of cyanobacterial toxins being confirmed both in vitro and in vivo [ 6 , 7 , 8 , 9 ], data on the cyanobacterial influence on the manifestation of diseases or on the susceptibility of individuals to bacterial and viral agents frequently present in the environment together with cyanobacteria, are sparse. A limited number of studies indicate that cyanobacteria may negatively contribute to the effects of other stressors.…”

Insight into Unprecedented Diversity of Cyanopeptides in Eutrophic Ponds Using an MS/MS Networking Approach

“…Microcystins are cyclic heptapeptides produced, among others, by Microcystis, Anabaena/Dolichospermum, Nodularia, and Oscillatoria . While the liver is the primary target of MCs, they are also a skin, eye, and throat irritants and immunomodulating agents [ 56 , 57 ]. Microcystin-LR was the first identified cyanotoxin and is the most studied.…”

Effects of cyanobacterial toxins on the human gastrointestinal tract and the mucosal innate immune system

“…Similarly to the GIT, cells of the innate immune system only express a limited set of OATPs. Transcriptomic analyses revealed high expression of OATP2B1 mRNA and lower levels of OATP3A1, 4A1, and 4C1, while no transcriptomic indication for OATP1A1, 1A5, 1B1, 1B2, 1B3, or 1C1 expression in human macrophages was found [68][69][70]. Furthermore, functional studies on drug transport via OATP2A1 and 2B1 in human macrophages indicate their functional expression [71,72].…”