Marine peptides as immunomodulators: Californiconus californicus-derived synthetic conotoxins induce IL-10 production by regulatory T cells (CD4+Foxp3+)

Zazueta-Favela, Daniela; Donis-Maturano, Luis; Licea-Navarro, Alexei F.; Bernáldez-Sarabia, Johanna; Dan, Kee W L; Cota-Arce, Julián M.; Escobedo, Galileo; León-Nava, Marco A. De

doi:10.1080/08923973.2019.1641114

Cited by 7 publications

(7 citation statements)

References 38 publications

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“…Although there are no data showing that α9α10 nAChRs in murine bone marrow granulocytes are constitutively active, we have previously shown effects of α9α10 antagonists, RgIA and Vc1.1 in the absence of agonists, on functions of murine bone marrow granulocytes ( Safronova et al, 2021 ). Similar results were obtained by other groups for the action of different nAChR antagonists on immune cells ( Razani-Boroujerdi et al, 2007 ; Zazueta-Favela et al, 2019 ). Together with previous findings ( Safronova et al, 2016 , 2021 ; Serov et al, 2021 ), this supports the participation of the α9 and/or α9α10 nAChR in the anti-inflammatory processes and might help to explain the analgesic action of compounds inhibiting this receptor.…”

Section: Discussionsupporting

confidence: 90%

Interaction of α9α10 Nicotinic Receptors With Peptides and Proteins From Animal Venoms

Tsetlin

Haufe

Safronova

et al. 2021

Front. Cell. Neurosci.

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Unlike most neuronal nicotinic acetylcholine receptor (nAChR) subunits, α7, α9, and α10 subunits are able to form functional homo- or heteromeric receptors without any β subunits. While the α7 subtype is widely distributed in the mammalian brain and several peripheral tissues, α9 and α9α10 nAChRs are mainly found in the cochlea and immune cells. α-Conotoxins that specifically block the α9α10 receptor showed anti-nociceptive and anti-hyperalgesic effects in animal models. Hence, this subtype is considered a drug target for analgesics. In contrast to the α9α10-selective α-conotoxins, the three-finger toxin α-bungarotoxin inhibits muscle-type and α7 nAChRs in addition to α9α10 nAChRs. However, the selectivity of α-neurotoxins at the α9α10 subtype was less intensively investigated. Here, we compared the potencies of α-conotoxins and α-neurotoxins at the human α9α10 nAChR by two-electrode voltage clamp analysis upon expression in Xenopus oocytes. In addition, we analyzed effects of several α9α10-selective α-conotoxins on mouse granulocytes from bone marrow to identify possible physiological functions of the α9α10 nAChR subtype in these cells. The α-conotoxin-induced IL-10 release was measured upon LPS-stimulation. We found that α-conotoxins RgIA, PeIA, and Vc1.1 enhance the IL-10 expression in granulocytes which might explain the known anti-inflammatory and associated analgesic activities of α9α10-selective α-conotoxins. Furthermore, we show that two long-chain α-neurotoxins from the cobra Naja melanoleuca venom that were earlier shown to bind to muscle-type and α7 nAChRs, also inhibit the α9α10 subtype at nanomolar concentrations with one of them showing a significantly slower dissociation from this receptor than α-bungarotoxin.

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Section: Discussionsupporting

confidence: 90%

Interaction of α9α10 Nicotinic Receptors With Peptides and Proteins From Animal Venoms

Tsetlin

Haufe

Safronova

et al. 2021

Front. Cell. Neurosci.

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“…Mecamylamine reverses the ant-inflammatory role of nicotine in the nAChR-mediated cholinergic pathway. a-conotoxins (5.5 mM) increases IL-10 production in Tregs and decreased IL-17 production in T cells (225). In PMA-activated macrophages, a-conotoxins upregulate the TNF-a and IL-6 in a concentration-dependent manner (226).…”

Section: Mecamylaminementioning

confidence: 99%

Cholinergic System and Its Therapeutic Importance in Inflammation and Autoimmunity

2021

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Neurological and immunological signals constitute an extensive regulatory network in our body that maintains physiology and homeostasis. The cholinergic system plays a significant role in neuroimmune communication, transmitting information regarding the peripheral immune status to the central nervous system (CNS) and vice versa. The cholinergic system includes the neurotransmitter\ molecule, acetylcholine (ACh), cholinergic receptors (AChRs), choline acetyltransferase (ChAT) enzyme, and acetylcholinesterase (AChE) enzyme. These molecules are involved in regulating immune response and playing a crucial role in maintaining homeostasis. Most innate and adaptive immune cells respond to neuronal inputs by releasing or expressing these molecules on their surfaces. Dysregulation of this neuroimmune communication may lead to several inflammatory and autoimmune diseases. Several agonists, antagonists, and inhibitors have been developed to target the cholinergic system to control inflammation in different tissues. This review discusses how various molecules of the neuronal and non-neuronal cholinergic system (NNCS) interact with the immune cells. What are the agonists and antagonists that alter the cholinergic system, and how are these molecules modulate inflammation and immunity. Understanding the various functions of pharmacological molecules could help in designing better strategies to control inflammation and autoimmunity.

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Section: Effects On Adaptive Immunitymentioning

confidence: 99%

“…Other toxins have been shown to stimulate the differentiation of lymphocyte subpopulations, such as those derived from the conotoxins of the marine snail Californiconus californicus called cal14.1b and cal14.2c [ 120 ]. These toxins interact with the α7 subunit of nACh receptors, which are abundantly expressed on Treg lymphocytes [ 120 ]. This interaction decreases the production of IL-17A and inhibits NF-κB signaling; therefore, this interaction has an impact on the production of cytokines such as IL-2, IFN-γ, IL-4 and TNF-α, inhibiting the Th1 and Th17 lymphocyte-dependent inflammatory responses that promote the development of cellular immunity and the risk of T cell-mediated autoimmune diseases [ 40 , 105 , 120 ].…”

Section: Effects On Adaptive Immunitymentioning

confidence: 99%

Biological Effects of Animal Venoms on the Human Immune System

Avalo

Barrera

Agudelo-Delgado

et al. 2022

Toxins

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Venoms are products of specialized glands and serve many living organisms to immobilize and kill prey, start digestive processes and act as a defense mechanism. Venoms affect different cells, cellular structures and tissues, such as skin, nervous, hematological, digestive, excretory and immune systems, as well as the heart, among other structures. Components of both the innate and adaptive immune systems can be stimulated or suppressed. Studying the effects on the cells and molecules produced by the immune system has been useful in many biomedical fields. The effects of venoms can be the basis for research and development of therapeutic protocols useful in the modulation of the immunological system, including different autoimmune diseases. This review focuses on the understanding of biological effects of diverse venom on the human immune system and how some of their components can be useful for the study and development of immunomodulatory drugs.

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Marine peptides as immunomodulators: Californiconus californicus-derived synthetic conotoxins induce IL-10 production by regulatory T cells (CD4⁺Foxp3⁺)

Cited by 7 publications

References 38 publications

Interaction of α9α10 Nicotinic Receptors With Peptides and Proteins From Animal Venoms

Interaction of α9α10 Nicotinic Receptors With Peptides and Proteins From Animal Venoms

Cholinergic System and Its Therapeutic Importance in Inflammation and Autoimmunity

Biological Effects of Animal Venoms on the Human Immune System

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