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Protein Tyrosine Phosphatases inhibition during allergen sensitization or allergen challenge prevents asthma development
Author(s) -
Pouliot Philippe,
Camateros Pierre,
Radzioch Danuta,
Olivier Martin
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.483
Subject(s) - sensitization , immunoglobulin e , allergen , immunology , protein tyrosine phosphatase , eosinophilia , medicine , allergy , phosphorylation , chemistry , antibody , biochemistry
Protein tyrosine kinases (PTKs) are crucial in the initiation of intracellular signalling events. Consequently, their activity is necessary for asthma development in mouse models. The role of PTK's counterparts, the protein tyrosine phosphatases (PTPs), was never carefully investigated. Interestingly, some of our previous results suggested that inhibition of PTPs favours a Th1 immune response. In the present study, we hypothesized that global inhibition of PTPs using peroxovanadiums during either allergen sensitization or allergen challenge could prevent asthma development. Our results show that inhibition during allergen sensitization reduced serum IgE levels, reduced lung eosinophilia and prevented development of airway hyperresponsiveness (AHR). Inhibition during lung allergen challenge resulted in similar data: decrease lung eosinophilia, and prevention of AHR, while serum IgE levels were unaffected. Peroxovanadium injection supported the expression of Th1 cytokines in the spleen and inhibited Th2 type cytokines expression, providing a mode of action for this inhibitor. Our results are the first demonstration of the necessity of functional PTP activity for allergic asthma development in both sensitization and allergen challenge phases. These data open the possibility for new therapeutic approaches aiming at specific PTPs. Support for this study was provided by the CIHR.