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Mol Immunol. 2016 Jul;75:144-50. doi: 10.1016/j.molimm.2016.05.017. Epub 2016 Jun 9.

Targeted inhibition of GATA-6 attenuates airway inflammation and remodeling by regulating caveolin-1 through TLR2/MyD88/NF-κB in murine model of asthma.

Author information

1
Respiratory Department, The Second Affiliated Hospital, Xi'an Jiaotong University School of Medicine, Xi'an 710004, Shaanxi, PR China. Electronic address: pingfangsx@163.com.
2
Respiratory Department, The Second Affiliated Hospital, Xi'an Jiaotong University School of Medicine, Xi'an 710004, Shaanxi, PR China.
3
Key Laboratory, Biochemical Information Engineering of Ministry of Education Xi'an Jiaotong University School of Life Science and Technology, Xi'an 710049, Shaanxi, PR China.

Abstract

The purpose of this study was to evaluate the effects of GATA-6 on airway inflammation and remodeling and the underlying mechanisms in a murine model of chronic asthma. Female BALB/c mice were randomly divided into four groups: phosphate-buffered saline control (PBS), ovalbumin (OVA)-induced asthma group (OVA), OVA+ siNC and OVA+ siGATA-6. In this mice model, GATA-6 expression level was significantly elevated and the expression in Caveolin-1 (Cav-1) inversely correlated with the abundance of GATA-6 in OVA-induced asthma of mice. Silencing of GATA-6 gene expression upregulated Cav-1 expression. Additionally, downregulation of GATA-6 dramatically decreased OVA-challenged inflammation, infiltration, and mucus production. Moreover, silencing of GATA-6 resulted in decreased levels of immunoglobulin E (IgE) and inflammatory mediators and reduced inflammatory cell accumulation, as well as inhibiting the expression of important mediators including matrix metalloproteinase (MMP)-2 and MMP-9, TGF-β1, and a disintegrin and metalloproteinase 8 (ADAM8) and ADAM33, which is related to airway remodeling. Further analysis confirmed that silencing of GATA-6 attenuated OVA-induced airway inflammation and remodeling through the TLR2/MyD88 and NF-κB pathway. In conclusion, these findings indicated that the downregulation of GATA-6 effectively inhibited airway inflammation and reversed airway remodeling via Cav-1, at least in part through downregulation of TLR2/MyD88/NF-κB, which suggests that GATA-6 represents a promising therapeutic strategy for human allergic asthma.

KEYWORDS:

Airway inflammation; Airway remodeling; Asthma; Caveolin-1 (Cav-1); GATA-6

PMID:
27289030
DOI:
10.1016/j.molimm.2016.05.017
[Indexed for MEDLINE]

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