Sticholysins, pore-forming proteins from a marine anemone can induce maturation of dendritic cells through a TLR4 dependent-pathway

The Important Role of Membrane Fluidity on the Lytic Mechanism of the α-Pore-Forming Toxin Sticholysin I

“…The action mechanism of actinoporins has been largely studied due to their biomedical interest [ 23 , 24 , 25 , 26 ]. These toxins are produced as soluble proteins that eventually bind to the lipid membrane where they undergo conformational changes leading to pore formation.…”

Marine natural products

“…The discovery, development, and utilisation of sea anemone neurotoxins in general, 595 and specifically regarding sticholysin toxins, 596 have been reviewed. Sticholysin II, and likely also its isoform sticholysin I, induce maturation of dendritic cells through a toll-like receptor 4/myeloid differentiation primary response gene 88-dependent pathway, 597 and that sticholysin II shares similar abilities to act as an immunostimulant to those of the evolutionarily distinct pore-forming peptide listeriolysin O (bacteria Listeria monocytogenes ). 598 Kunitz-type peptides from the sea anemone Heteractis crispa protect neuronal cells from the toxic effects of 6-hydroxydopamine.…”

Marine Pharmacology in 2019‐2021: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti‐Inflammatory, Antiprotozoal, Antituberculosis and Antiviral Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action

“…Secondly, Lin and colleagues reported that the cembranoid terpenoid crassolide (85), isolated from the soft coral Sarcophyton crassocaule, also negatively impacted LPS-induced activation of dendritic cells and downstream T cell responses in vitro, and these effects therapeutically attenuated the development of autoantibodies and associated thrombosis in vivo [100]. In contrast, Laborde and colleagues showed that the large pore-forming proteins sticholysins I and II, purified from the marine anemone Stichodactyla helianthus, enhanced bone marrow-derived dendritic cell maturation through a TLR4-specific manner that resulted in enhanced activation of CD8+ cytotoxic T cells [109]. Finally, Manzo and colleagues characterized an "unprecedented" polyketide phosphatidylmonogalactosyldiacylglycerol pool (91), uncovered in the marine diatom Thalassiosira weissflogii, which was also immunostimulatory to dendritic cells by acting directly as a TLR4 agonist that increased the ability of these cells to activate CD8+ T cells [110].…”

“…Moreover, Wu and colleagues showed that fucoxanthin (43) binds to Kelch-like ECH-associated protein 1 (Keap1), a Nrf2 inhibitor and sensor of oxidative stress, at the same binding site as Nrf2 thus enhancing Nrf2/ARE signaling in PC12 cells [132]. Kalina and colleagues described the APETx-like peptides Hcr 1b-2, Hcr 1b-3, and Hcr 1b-4 (109)(110)(111), discovered in the sea anemone Heteractis crispa, that inhibited rat acidsensing ion channel (rASIC) 1a that is highly expressed in the central nervous system. Rat ASIC1a was expressed in Xenopus laevis oocytes and Hcr 1b-3 and -4 (109-110) reversibly inhibited the channel in a dose-dependent manner, indicating therapeutic potential for pathological conditions associated with prolonged acidosis including PD, multiple sclerosis, epilepsy, and ischemic stroke [133].…”