Venom components of the scorpion Centruroides limpidus modulate cytokine expression by T helper lymphocytes: Identification of ion channel-related toxins by mass spectrometry.

Autor: Cota-Arce JM; Departamento de Innovación Biomédica, Centro de Investigación Científica y de Educación Superior de Ensenada (CICESE), Baja California, C.P. 22860, México., Zazueta-Favela D; Departamento de Innovación Biomédica, Centro de Investigación Científica y de Educación Superior de Ensenada (CICESE), Baja California, C.P. 22860, México., Díaz-Castillo F; Departamento de Innovación Biomédica, Centro de Investigación Científica y de Educación Superior de Ensenada (CICESE), Baja California, C.P. 22860, México., Jiménez S; Departamento de Innovación Biomédica, Centro de Investigación Científica y de Educación Superior de Ensenada (CICESE), Baja California, C.P. 22860, México., Bernáldez-Sarabia J; Departamento de Innovación Biomédica, Centro de Investigación Científica y de Educación Superior de Ensenada (CICESE), Baja California, C.P. 22860, México., Caram-Salas NL; Departamento de Innovación Biomédica, Centro de Investigación Científica y de Educación Superior de Ensenada (CICESE), Baja California, C.P. 22860, México; Cátedra CONACYT/Departamento de Innovación Biomédica, CICESE, México., Dan KWL; Departamento de Innovación Biomédica, Centro de Investigación Científica y de Educación Superior de Ensenada (CICESE), Baja California, C.P. 22860, México., Escobedo G; Laboratorio de Proteómica y Metabolómica, Dirección de Investigación, Hospital General de México 'Dr. Eduardo Liceaga', Ciudad de México, C.P. 06720, México., Licea-Navarro AF; Departamento de Innovación Biomédica, Centro de Investigación Científica y de Educación Superior de Ensenada (CICESE), Baja California, C.P. 22860, México., Possani LD; Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, C.P. 62210, México., De León-Nava MA; Departamento de Innovación Biomédica, Centro de Investigación Científica y de Educación Superior de Ensenada (CICESE), Baja California, C.P. 22860, México. Electronic address: madeleon@cicese.mx.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2020 Jul; Vol. 84, pp. 106505. Date of Electronic Publication: 2020 May 04.
DOI: 10.1016/j.intimp.2020.106505
Abstrakt: The study of the effector mechanisms of T helper cells has revealed different phenotypic characteristics that can be manipulated for designing new therapeutic schemes in different pathological scenarios. Ion channels are significant targets in T lymphocyte modulation since they are closely related to their effector activity. Remarkably, some toxins produced by scorpions specifically affect the function of these membrane proteins. For that reason, these toxins are important candidates in the search for new immunomodulators. Here, the effect of two venom fractions of the scorpion Centruroides limpidus was assessed on T lymphocyte proliferation and cytokine production. The venom fractions ClF8 and ClF9 were separated by reversed-phase high-performance liquid chromatography (RP-HPLC) and cultured at 25 and 35 µg/ml with murine T lymphocytes. The results indicate that the fraction ClF8 increased both production and secretion levels of IFN-γ, IL-4, IL-17A and IL-10 by CD4 + T cells at 24 h. In contrast, fraction ClF9 only promoted the secretion of IL-17A and IL-10 at its highest concentration (35 µg/ml). Both fractions did not show any effect on T cell proliferation. Subsequent analyses by liquid chromatography-tandem mass spectrometry (LC-MS/MS) revealed seventeen toxins in the fraction ClF8 and five toxins in the fraction ClF9, most of them with voltage-gated sodium (NaScTx) and potassium (KScTx) channels as molecular targets. These toxins might probably interact with ion channels involved in T lymphocyte activity. Our findings suggest that the difference in composition between the two fractions could be related to the observed effects, and the components identified could be isolated to search for possible immunomodulatory molecules.
Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest in this work.
(Copyright © 2020 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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