Bcl11b Regulates IL-17 Through the TGF-β/Smad Pathway in HDM-Induced Asthma
Allergy, Asthma & Immunology Research
;
: 543-554, 2018.
Article
in English
| 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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Phosphorylation
/
Plasma
/
Plasmids
/
Asthma
/
RNA, Messenger
/
Enzyme-Linked Immunosorbent Assay
/
T-Lymphocytes
/
Transforming Growth Factors
/
Blotting, Western
/
Polymerase Chain Reaction
Limits:
Animals
/
Humans
Language:
English
Journal:
Allergy, Asthma & Immunology Research
Year:
2018
Type:
Article
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