Dataset Information

Posttranscriptional Regulation of Interleukin-33 Expression by MicroRNA-200 in Bronchial Asthma.

ABSTRACT: The importance of understanding how interleukin-33 (IL-33) is regulated (particularly by miRs) is critical in IL-33 biology, and evidence of this in asthma pathology is limited. MicroRNA profiling of cells isolated from bronchoalveolar lavage of 14 asthmatic patients and 11 healthy controls revealed miR-200b and miR-200c were significantly reduced in asthmatic patients compared with healthy controls. The reduction was validated in two independent models of allergen-induced allergic airway inflammation and further demonstrated to be inversely correlated with asthma severity, as well as increased IL-33 production in asthmatic patients. In addition, the miR-200b and miR-200c binding sites in the 3' UTR of IL-33 mRNA were identified by bioinformatics analysis and reporter gene assay. More importantly, introduction of miR-200b and miR-200c reduced, while inhibition of endogenous miR-200b and miR-200c increased, the induction of IL-33 expression in lung epithelial cells. Exogenous administration of miR-200b to lungs of mice with allergic inflammation resulted in a decrease in IL-33 levels and resolution of airway inflammation phenotype. In conclusion, miR-200b and miR-200c by regulating the expression of IL-33 have a role in bronchial asthma, and dysregulation of expression of miR-200b/c may be the underlying mechanism resulting in the asthmatic phenotype.

SUBMITTER: Tang X

PROVIDER: S-EPMC6035355 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Posttranscriptional Regulation of Interleukin-33 Expression by MicroRNA-200 in Bronchial Asthma.

Tang Xin X Wu Feng F Fan Jinshuo J Jin Yang Y Wang Jianjun J Yang Guanghai G

Molecular therapy : the journal of the American Society of Gene Therapy 20180425 7

The importance of understanding how interleukin-33 (IL-33) is regulated (particularly by miRs) is critical in IL-33 biology, and evidence of this in asthma pathology is limited. MicroRNA profiling of cells isolated from bronchoalveolar lavage of 14 asthmatic patients and 11 healthy controls revealed miR-200b and miR-200c were significantly reduced in asthmatic patients compared with healthy controls. The reduction was validated in two independent models of allergen-induced allergic airway inflam ...[more]

PMID: 29778524

Similar Datasets

Project description:Asthma exacerbations are commonly associated with rhinovirus (RV) infection. Interleukin-33 (IL-33) plays an important role during exacerbation by enhancing Type 2 inflammation. Recently we showed that RV infects bronchial smooth muscle cells (BSMCs) triggering production of interferons and IL-33. Here we compared levels of RV-induced IL-33 in BSMCs from healthy and asthmatic subjects, and explored the involvement of pattern-recognition receptors (PRRs) and downstream signalling pathways in IL-33 expression. BSMCs from healthy and severe and non-severe asthmatic patients were infected with RV1B or stimulated with the PRR agonists poly(I:C) (Toll-like receptor 3 (TLR3)), imiquimod (TLR7) and poly(I:C)/LyoVec (retinoic acid-inducible gene 1 (RIG-I)/melanoma differentiation-associated protein 5 (MDA5)). Knockdown of TLR3, RIG-I and MDA5 was performed, and inhibitors targeting TBK1, nuclear factor-κB (NF-κB) and transforming growth factor (TGF)-β-activated kinase 1 (TAK1) were used. Gene and protein expression were assessed. RV triggered IL-33 gene and protein expression in BSMCs. BSMCs from patients with non-severe asthma showed higher baseline and RV-induced IL-33 gene expression compared to cells from patients with severe asthma and healthy controls. Furthermore, RV-induced IL-33 expression in BSMCs from healthy and asthmatic individuals was attenuated by knockdown of TLR3. Inhibition of TAK1, but not NF-κB or TBK1, limited RV-induced IL-33. The cytokine secretion profile showed higher production of IL-33 in BSMCs from patients with non-severe asthma compared to healthy controls upon RV infection. In addition, BSMCs from patients with non-severe asthma had higher levels of RV-induced IL-8, TNF-α, IL-1β, IL-17A, IL-5 and IL-13. RV infection caused higher levels of IL-33 and increased pro-inflammatory and Type 2 cytokine release in BSMCs from patients with non-severe asthma. RV-induced IL-33 expression was mainly regulated by TLR3 and downstream via TAK1. These signalling molecules represent potential therapeutic targets for treating asthma exacerbations.

Project description:Abstract Background Previous studies reported that patients with asthma showed higher levels of interleukin (IL)‐33 in peripheral blood, compared to healthy control (HCs). However, we also noticed that there were no significant differences of IL‐33 levels between controls and asthma patients in a recent study. We aim to conduct this meta‐analysis and evaluate the feasibility of IL‐33 in peripheral blood that may act as a promising biomarker in asthma. Methods Articles published before December 2022 were searched in these databases (PubMed, Web of Science, EMBASE, and Google Scholar). We used STATA 12.0 software to compute the results. Results The study showed that asthmatics showed higher IL‐33 level in serum and plasma, compared to HCs (serum: standard mean difference [SMD] 2.06, 95% confidence interval [CI] 1.12−3.00, I2 = 98.4%, p < .001; plasma: SMD 3.67, 95% CI 2.32−5.03, I2 = 86.0%, p < .001). Subgroup analysis indicated that asthma adults showed higher IL‐33 level in serum, compared to HCs, whereas no significant difference in IL‐33 level in serum was showed between asthma children and HCs (adults: SMD 2.17, 95% CI 1.09−3.25; children: SMD 1.81, 95% CI −0.11 to 3.74). The study indicated that moderate and severe asthmatics showed higher IL‐33 level in serum, compared to mild asthmatics (SMD 0.78, 95% CI 0.41−1.16, I2 = 66.2%, p = .011). Conclusions In conclusion, the main findings of present meta‐analysis suggested that there was a significant correlation between IL‐33 levels and the severity of asthma. Therefore, IL‐33 levels of either serum or plasma may be regarded as a useful biomarker of asthma or the degree of disease. In conclusion, the main findings of present meta‐analysis suggested that there was significant correlation between interleukin (IL)‐33 levels and the severity of asthma. Therefore, the IL‐33 levels of either serum or plasma may be regarded as a useful biomarker of asthma or the degree of disease. However, we can not ignore the influences of ethnic and age factors on the IL‐33 levels. It is encouraged that data from multi‐center, well‐designed and large sample size studies should be conducted for validating the clinical value of IL‐33 on asthma.

Dataset Information

Posttranscriptional Regulation of Interleukin-33 Expression by MicroRNA-200 in Bronchial Asthma.

Publications

Posttranscriptional Regulation of Interleukin-33 Expression by MicroRNA-200 in Bronchial Asthma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets