DZNep attenuates allergic airway inflammation in an ovalbumin-induced murine model.

Abstract

BACKGROUND:

Growing evidence shows that enhancer of zeste homolog 2 (EZH2) plays a role in various physiological functions and cancer pathogenesis. However, its contribution to allergic diseases remains controversial. We sought to investigate the role of EZH2 in the pathogenesis of allergic airway inflammation.

METHODS:

3-Deazaneplanocin A (DZNep), an indirect inhibitor of EZH2, was administered via intraperitoneal injection in an ovalbumin (OVA)-induced murine model of allergic airway inflammation. The expression of EZH2 in the allergic airway tissues was examined by immunohistochemistry (IHC) and western blot. The inflammatory cell infiltration and the goblet cell hyperplasia in the murine nose and lung were detected by hematoxylin and eosin (H&E) staining and periodic acid-Schiff (PAS) staining. Levels of cytokines, including IL-4, IFN-γ, IL-6, and IL-10, were evaluated in the bronchoalveolar lavage fluid (BALF) using Enzyme-linked immune sorbent assay (ELISA).

RESULTS:

EZH2 expression was inhibited by DZNep treatment (P < 0.05). The administration of DZNep significantly inhibited the inflammatory cell infiltration (P < 0.0001) and goblet cell hyperplasia (P < 0.001). Moreover, it suppressed the secretion of IL-4 (P < 0.0001) and IL-6 (P < 0.01) in the BALF.

CONCLUSIONS:

Our findings demonstrate that DZNep attenuates allergic airway inflammation and could be a new therapeutic option for allergic rhinitis and asthma.

• Authors: Hang Li, Jian Li, Tong Lu, Dehua Chen, Rui Xu, Wei Sun, Xi Luo, Huabin Li, Renqiang Ma, Weiping Wen
• Journal: Molecular immunology (Mol Immunol) Vol. 131 Pg. 60-67 (03 2021) ISSN: 1872-9142 [Electronic] England
• PMID: 33358566 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier Ltd. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Cytokines
• 3-deazaneplanocin
• Ovalbumin
• Adenosine

Topics

• Adenosine (analogs & derivatives, pharmacology)
• Animals
• Anti-Inflammatory Agents (pharmacology)
• Asthma (chemically induced, drug therapy, metabolism)
• Bronchoalveolar Lavage Fluid
• Cytokines (metabolism)
• Disease Models, Animal
• Female
• Hypersensitivity (drug therapy, metabolism)
• Inflammation (chemically induced, drug therapy, metabolism)
• Lung (drug effects, metabolism)
• Mice
• Mice, Inbred BALB C
• Ovalbumin (pharmacology)