Skip to Main content Skip to Navigation
New interface
Theses

Asthme allergique induit par un allergène d’acarien, House Dust Mite (HDM) : rôles de la caspase-1 et de la protéine kinase C thêta (PKC-θ)

Abstract : Studies from our laboratory have shown a critical role of NLRP3 inflammasome in response to ovalbumin allergen. In the present study we investigate the role of NLRP3 and caspase-1 in a mouse model of pulmonary inflammation induced by HDM. We have shown a regulatory role of caspase-1 dependant of the NLRP3 inflammasome and the adaptator molecule ASC but not NLRC4. The regulation of the allergic response is characterized by an increase of eosinophilia, bronchial hyperreactivity and Th2 cytokines production (IL-4, IL-5, IL-13 and IL-33) in lungs. We have shown that mechanisms responsible of this regulation are associated with IL-33 production by macrophages and that neutralization of IL-33 by local administration of a fusion protein of the ST2 receptor (muST2-Fc) reduce characteristics of asthma. These results suggest that caspase-1 activation reduce IL-33 production in vivo regulating lung inflammation and Th2 response induced by HDM. Moreover, we investigate the role of the Protein Kinase C theta (PKC-θ) in allergic airway inflammation. We have demonstrated that PKC-θ plays a protective role in allergic asthma but is critical for the activation and proliferation of innate lymphoid cells (ILC2). In addition, in vivo inhibition by oral administration of PKC-θ specific inhibitor C20 (BIX02656) reduces pulmonary inflammation with IL-5 and IL-13 production. We suggest that PKC-θ is implicated in Th2 and ILC2 differenciation by a mechanism dependant on transcription factors IRF4 and NFAT-1. Finally, my thesis projects describe IL-33 and PKC-θ as potential therapeutic targets for allergic lung inflammation.
Document type :
Theses
Complete list of metadata

Cited literature [277 references]  Display  Hide  Download

https://tel.archives-ouvertes.fr/tel-01374855
Contributor : ABES STAR :  Contact
Submitted on : Sunday, October 2, 2016 - 1:05:11 AM
Last modification on : Wednesday, August 24, 2022 - 11:38:10 AM
Long-term archiving on: : Tuesday, January 3, 2017 - 12:20:24 PM

File

fahima-madouri_3673.pdf
Version validated by the jury (STAR)

Identifiers

  • HAL Id : tel-01374855, version 1

Collections

Citation

Fahima Madouri. Asthme allergique induit par un allergène d’acarien, House Dust Mite (HDM) : rôles de la caspase-1 et de la protéine kinase C thêta (PKC-θ). Allergologie. Université d'Orléans, 2014. Français. ⟨NNT : 2014ORLE2055⟩. ⟨tel-01374855⟩

Share

Metrics

Record views

243

Files downloads

658