Bcl11b Regulates IL-17 Through the TGF-β/Smad Pathway in HDM-Induced Asthma
Allergy, Asthma & Immunology Research
;
: 543-554, 2018.
Article
Dans Anglais
| WPRIM
| ID: wpr-716677
ABSTRACT
PURPOSE:
T helper (Th) 17 cells play a critical role in the development of asthma, but the underlying mechanism of how interleukin (IL)-17 is regulated in allergic airway inflammation is poorly understood. In this study, we investigated the impact of Bcl11b on Th17 response in asthma.METHODS:
Blood samples from patients with mild asthma (MA) and severe asthma (SA) were collected. Expression of Bcl11b, IL-4, IL-5, IL-13, IL-17A and transforming growth factor (TGF)-β1 were determined in CD4+ T cells and plasma by polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Relative mRNA and protein levels of Bcl11b, IL-17A and genes involved in the TGF/Smad signaling pathway were examined by PCR, ELISA and western blot analysis in house dust mite (HDM)-challenged mice. Ectopic expression of Bcl11b in HDM-stimulated primary mouse splenocytes was achieved by nucleofection of Bcl11b expression plasmid.RESULTS:
We found significantly decreased Bcl11b but increased IL-17A and TGF-β1 expression in patients with asthma and a strongly negative correlation between Bcl11b and these 2 cytokines in SA patients. Similar expression patterns of Bcl11b, IL-17A and TGF-β1 were also found in mice with HDM-induced allergic airway inflammation. We demonstrated further that Smad2/3 phosphorylation was increased in HDM-challenged mice and that ectopic expression of Bcl11b in HDM-stimulated primary mouse splenocytes reduced Smad2 phosphorylation and IL-17 expression.CONCLUSIONS:
Our findings demonstrate a potential effect of Bc111b in controlling IL-17-mediated inflammation in asthma and suggest that Bc111b may be a useful therapeutic target for asthma.
Texte intégral:
Disponible
Indice:
WPRIM (Pacifique occidental)
Sujet Principal:
Phosphorylation
/
Plasma sanguin
/
Plasmides
/
Asthme
/
ARN messager
/
Test ELISA
/
Lymphocytes T
/
Facteurs de croissance transformants
/
Technique de Western
/
Réaction de polymérisation en chaîne
Limites du sujet:
Animaux
/
Humains
langue:
Anglais
Texte intégral:
Allergy, Asthma & Immunology Research
Année:
2018
Type:
Article
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