CD4 T lymphocytes are able to differentiate into distinct subtypes according to several immunological scenarios, including T helper (Th)1, Th2, Th17 and regulatory T (Treg) cells. CD4 T cells are phenotypically flexible and have specific ion channels, such as the nicotinic acetylcholine receptors (nAChR) that could be modulated by peptides produced by marine snails, known as conotoxins. Their effect on T lymphocytes has not been explored and emerging evidence suggests that these peptides may have immunomodulatory activities. This study investigated the effect of two -derived synthetic conotoxins on the proliferation and differentiation of T lymphocyte subpopulations Th1, Th2, Th17 and Treg. Cells from lymph nodes of BALB/c mice were cultured in the presence of conotoxins cal14.1b and cal14.2c (5.5 μM), during 96 h. Cell proliferation and intracellular cytokine production (IFN-γ, IL-4, IL-17 and IL-10) were analyzed by flow cytometry. cal14.1b and cal14.2c increased intracellular IL-10 production in Treg (CD3CD4Foxp3) cells and decreased intracellular IL-17 production (CD3CD4) after 72 h of culture. Conotoxins did not show any effect on T cell proliferation nor Th1/Th2 balance. These results suggest that synthetic conotoxins exert immunomodulatory activity, especially by regulating specific functions on T lymphocytes.
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http://dx.doi.org/10.1080/08923973.2019.1641114 | DOI Listing |
ACS Pharmacol Transl Sci
December 2024
School of Biological Sciences, University of Utah, Salt Lake City, Utah 84112, United States.
Nicotinic acetylcholine receptors containing the α9 subunit have been mechanistically implicated in alleviating chemotherapy-induced neuropathic pain. However, the cell types that underlie these effects are currently unknown. RgIA-5474 is a recently developed, synthetic α-conotoxin analog that is a potent antagonist of human α9α10 nAChRs.
View Article and Find Full Text PDFToxins (Basel)
November 2024
Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
Conotoxins are small and highly potent neurotoxic peptides derived from the venom of marine cone snails which have captured the interest of the scientific community due to their pharmacological potential. These toxins display significant sequence and structure diversity, which results in a wide range of specificities for several different ion channels and receptors. Despite the recognized importance of these compounds, our ability to determine their binding targets and toxicities remains a significant challenge.
View Article and Find Full Text PDFEur J Med Chem
January 2025
Centre for Pain Research, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland, 4067, Australia.
Conotoxins, isolated from the venom of carnivorous marine snails of the Conus genus, are disulfide-rich peptides and proteins with well-defined three-dimensional structures. Conotoxins' ability to target a wide range of ion channels and receptors, including voltage- and ligand-gated ion channels, G protein-coupled receptors, monoamine transporters, and enzyme, at exquisite potency and selectivity make them valuable research and therapeutic tools. Despite their potentials, Conus venom peptides are present in limited quantities in nature and possess structural complexity that raises significant synthetic challenges for both chemical synthesis and recombinant expression.
View Article and Find Full Text PDFToxicon
November 2024
Department of Chemistry, School of Chemical Sciences, Central University of Karnataka, Kalaburagi, 585367, Karnataka, India. Electronic address:
Implementation of the next-generation technologies for gene sequencing of venom duct transcriptome has provided a large number of peptide sequences of marine cone snails. Emerging technologies on computational platforms are now rapidly evolving for the accurate predictions of the 3D structure of the polypeptide using the primary sequence. The current report aims to integrate the information derived from these two technologies to develop the concept of structure-aided function assignment of Conus peptides.
View Article and Find Full Text PDFPharmacol Rev
August 2024
Guangxi Key Laboratory of Special Biomedicine, School of Medicine, Guangxi University, Nanning, China (S.P., N.W., Z.M., D.Z., X.Z., S.L.); Key Laboratory of Tropical Biological Resources of Ministry of Education, Hainan University, Haikou, China (D.Z., S.L.); Institute for Molecular Bioscience, Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science, The University of Queensland, Brisbane, Queensland, Australia (D.J.C.); Departments of Biology and Psychiatry, University of Utah, Salt Lake City, Utah (J.M.M.); and George E. Wahlen Veterans Affairs Medical Center, Salt Lake City, Utah (J.M.M.)
Voltage-gated sodium (Na) channels are intimately involved in the generation and transmission of action potentials, and dysfunction of these channels may contribute to nervous system diseases, such as epilepsy, neuropathic pain, psychosis, autism, and cardiac arrhythmia. Many venom peptides selectively act on Na channels. These include conotoxins, which are neurotoxins secreted by cone snails for prey capture or self-defense but which are also valuable pharmacological tools for the identification and/or treatment of human diseases.
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