Dataset Information

Blockade of Mbd2 by siRNA-loaded liposomes protects mice against OVA-induced allergic airway inflammation via repressing M2 macrophage production.

ABSTRACT:

Objective

To address the role of methyl-CpG-binding domain 2 (MBD2) in the pathogenesis of asthma and its potential as a target for the asthmatic therapy.

Methods

Studies were conducted in asthmatic patients and macrophage-specific Mbd2 knockout mice to dissect the role of MBD2 in asthma pathogenesis. Additionally, RNAi-based therapy with Mbd2 siRNA-loaded liposomes was conducted in an ovalbumin (OVA)-induced allergic airway inflammation mouse model.

Results

Asthmatic patients and mice challenged with OVA exhibited upregulated MBD2 expression in macrophages, especially in alternatively activated (M2) macrophages. In particular, macrophage-specific knockout of Mbd2 protected mice from OVA-induced allergic airway inflammation and suppressed the M2 program. Notably, intratracheal administration of liposomes carrying Mbd2 siRNA decreased the expression of Mbd2 and prevented OVA-induced allergic airway inflammation in mice, as indicated by the attenuated airway inflammation and mucus production.

Conclusions

The above data indicate that Mbd2 implicates in the pathogenesis of asthma predominantly by regulating the polarization of M2 macrophages, which supports that Mbd2 could be a viable target for treatment of asthma in clinical settings.

SUBMITTER: Wu GR

PROVIDER: S-EPMC9453648 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Blockade of Mbd2 by siRNA-loaded liposomes protects mice against OVA-induced allergic airway inflammation <i>via</i> repressing M2 macrophage production.

Wu Guo-Rao GR Zhou Min M Wang Yi Y Zhou Qing Q Zhang Lei L He Long L Zhang Shu S Yu Qilin Q Xu Yongjian Y Zhao Jianping J Xiong Weining W Wang Cong-Yi CY

Frontiers in immunology 20220825

<h4>Objective</h4>To address the role of methyl-CpG-binding domain 2 (MBD2) in the pathogenesis of asthma and its potential as a target for the asthmatic therapy.<h4>Methods</h4>Studies were conducted in asthmatic patients and macrophage-specific <i>Mbd2</i> knockout mice to dissect the role of MBD2 in asthma pathogenesis. Additionally, RNAi-based therapy with <i>Mbd2</i> siRNA-loaded liposomes was conducted in an ovalbumin (OVA)-induced allergic airway inflammation mouse model.<h4>Results</h4>A ...[more]

PMID: 36090987

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