RT Journal Article
T1 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
A1 López Rodríguez, Juan Carlos
A1 Manosalva, Juliana
A1 Cabrera-García, J. Daniel
A1 Escribese, María M.
A1 Villalba, Mayte
A1 Barber, Domingo
A1 Martínez Ruiz, Antonio
A1 Batanero Cremades, Eva
AB 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 p1-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 cysteineprotease activity, which may have important clinical implications for immune response to this aeroallergen in genetically susceptible individuals.
SN 2213-2317
YR 2019
FD 2019-09
LK https://hdl.handle.net/20.500.14352/102830
UL https://hdl.handle.net/20.500.14352/102830
LA eng
NO Spanish Government
NO European Union ERDF
DS Docta Complutense
RD 28 jul 2024