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Human glutathione-S-transferase pi potentiates the cysteine-protease activity of the Der p 1 allergen from house dust mite through a cysteine redox mechanism

Environmental proteases have been widely associated to the pathogenesis of allergic disorders. Der p 1, a cysteine-protease from house dust mite (HDM) Dermatophagoides pteronyssinus, constitutes one of the most clinically relevant indoor aeroallergens worldwide. Der p 1 protease activity depends on...

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Autores principales: López-Rodríguez, Juan Carlos, Manosalva, Juliana, Cabrera-García, J. Daniel, Escribese, María M., Villalba, Mayte, Barber, Domingo, Martínez-Ruiz, Antonio, Batanero, Eva
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6597738/
https://www.ncbi.nlm.nih.gov/pubmed/31229842
http://dx.doi.org/10.1016/j.redox.2019.101256
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author López-Rodríguez, Juan Carlos
Manosalva, Juliana
Cabrera-García, J. Daniel
Escribese, María M.
Villalba, Mayte
Barber, Domingo
Martínez-Ruiz, Antonio
Batanero, Eva
author_facet López-Rodríguez, Juan Carlos
Manosalva, Juliana
Cabrera-García, J. Daniel
Escribese, María M.
Villalba, Mayte
Barber, Domingo
Martínez-Ruiz, Antonio
Batanero, Eva
author_sort López-Rodríguez, Juan Carlos
collection PubMed
description Environmental proteases have been widely associated to the pathogenesis of allergic disorders. Der p 1, a cysteine-protease from house dust mite (HDM) Dermatophagoides pteronyssinus, constitutes one of the most clinically relevant indoor aeroallergens worldwide. Der p 1 protease activity depends on the redox status of its catalytic cysteine residue, which has to be in the reduced state to be active. So far, it is unknown whether Der p 1-protease activity could be regulated by host redox microenvironment once it reaches the lung epithelial lining fluid in addition to endogenous mite components. In this sense, Glutathione-S-transferase pi (GSTpi), an enzyme traditionally linked to phase II detoxification, is highly expressed in human lung epithelial cells, which represent the first line of defence against aeroallergens. Moreover, GSTpi is a generalist catalyst of protein S-glutathionylation reactions, and some polymorphic variants of this enzyme has been associated to the development of allergic asthma. Here, we showed that human GSTpi increased the cysteine-protease activity of Der p 1, while GSTmu (the isoenzyme produced by the mite) did not alter it. GSTpi induces the reduction of Cys residues in Der p 1, probably by rearranging its disulphide bridges. Furthermore, GSTpi was detected in the apical medium collected from human bronchial epithelial cell cultures, and more interesting, it increased cysteine-protease activity of Der p 1. Our findings support the role of human GSTpi from airways in modulating of Der p 1 cysteine-protease activity, which may have important clinical implications for immune response to this aeroallergen in genetically susceptible individuals.
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spelling pubmed-65977382019-07-11 Human glutathione-S-transferase pi potentiates the cysteine-protease activity of the Der p 1 allergen from house dust mite through a cysteine redox mechanism López-Rodríguez, Juan Carlos Manosalva, Juliana Cabrera-García, J. Daniel Escribese, María M. Villalba, Mayte Barber, Domingo Martínez-Ruiz, Antonio Batanero, Eva Redox Biol Research Paper Environmental proteases have been widely associated to the pathogenesis of allergic disorders. Der p 1, a cysteine-protease from house dust mite (HDM) Dermatophagoides pteronyssinus, constitutes one of the most clinically relevant indoor aeroallergens worldwide. Der p 1 protease activity depends on the redox status of its catalytic cysteine residue, which has to be in the reduced state to be active. So far, it is unknown whether Der p 1-protease activity could be regulated by host redox microenvironment once it reaches the lung epithelial lining fluid in addition to endogenous mite components. In this sense, Glutathione-S-transferase pi (GSTpi), an enzyme traditionally linked to phase II detoxification, is highly expressed in human lung epithelial cells, which represent the first line of defence against aeroallergens. Moreover, GSTpi is a generalist catalyst of protein S-glutathionylation reactions, and some polymorphic variants of this enzyme has been associated to the development of allergic asthma. Here, we showed that human GSTpi increased the cysteine-protease activity of Der p 1, while GSTmu (the isoenzyme produced by the mite) did not alter it. GSTpi induces the reduction of Cys residues in Der p 1, probably by rearranging its disulphide bridges. Furthermore, GSTpi was detected in the apical medium collected from human bronchial epithelial cell cultures, and more interesting, it increased cysteine-protease activity of Der p 1. Our findings support the role of human GSTpi from airways in modulating of Der p 1 cysteine-protease activity, which may have important clinical implications for immune response to this aeroallergen in genetically susceptible individuals. Elsevier 2019-06-11 /pmc/articles/PMC6597738/ /pubmed/31229842 http://dx.doi.org/10.1016/j.redox.2019.101256 Text en © 2019 The Authors. Published by Elsevier B.V. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Paper
López-Rodríguez, Juan Carlos
Manosalva, Juliana
Cabrera-García, J. Daniel
Escribese, María M.
Villalba, Mayte
Barber, Domingo
Martínez-Ruiz, Antonio
Batanero, Eva
Human glutathione-S-transferase pi potentiates the cysteine-protease activity of the Der p 1 allergen from house dust mite through a cysteine redox mechanism
title Human glutathione-S-transferase pi potentiates the cysteine-protease activity of the Der p 1 allergen from house dust mite through a cysteine redox mechanism
title_full Human glutathione-S-transferase pi potentiates the cysteine-protease activity of the Der p 1 allergen from house dust mite through a cysteine redox mechanism
title_fullStr Human glutathione-S-transferase pi potentiates the cysteine-protease activity of the Der p 1 allergen from house dust mite through a cysteine redox mechanism
title_full_unstemmed Human glutathione-S-transferase pi potentiates the cysteine-protease activity of the Der p 1 allergen from house dust mite through a cysteine redox mechanism
title_short Human glutathione-S-transferase pi potentiates the cysteine-protease activity of the Der p 1 allergen from house dust mite through a cysteine redox mechanism
title_sort human glutathione-s-transferase pi potentiates the cysteine-protease activity of the der p 1 allergen from house dust mite through a cysteine redox mechanism
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6597738/
https://www.ncbi.nlm.nih.gov/pubmed/31229842
http://dx.doi.org/10.1016/j.redox.2019.101256
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