Myeloid differentiation protein‐2 has a protective role in house dust mite‐mediated asthmatic characteristics with the proinflammatory regulation of airway epithelial cells and dendritic cells.

Autor: Ishii, Takashi, Murakami, Yusuke, Narita, Tomoya, Nunokawa, Hiroki, Miyake, Kensuke, Nagase, Takahide, Yamashita, Naomi
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Zdroj: Clinical & Experimental Allergy; Jan2022, Vol. 52 Issue 1, p149-161, 13p, 1 Chart, 6 Graphs
Abstrakt: Background: Myeloid differentiation protein‐2 (MD‐2) is a lipopolysaccharide‐binding protein involved in lipopolysaccharide signalling via Toll‐like receptor 4 (TLR4). TLR4 plays an essential role in HDM‐mediated allergic airway inflammation. Moreover, MD‐2 is structurally similar to Der f 2, a major allergen from house dust mite (HDM). Objectives: We aimed to clarify the role of MD‐2 in the pathogenesis of HDM‐mediated allergic airway inflammation. Methods: Wild‐type (WT), TLR4 knockout and MD‐2 knockout mice were subjected to intranasal instillation of HDM extract, and asthmatic features were evaluated. We also evaluated gene sets regulated by MD‐2 in HDM‐treated airway epithelial cells and examined the function of dendritic cells from lymph nodes and from lungs. Results: Aggravated allergic airway inflammation with increased airway hyperresponsiveness was observed in MD‐2 knockout mice compared with WT and TLR4 knockout mice. Global gene expression analysis revealed an MD‐2 regulated proinflammatory response and reconstituted TLR4 signalling in airway epithelial cells. The ability of dendritic cells to evoke an allergic immune response was enhanced in MD‐2 knockout mice. Conclusions & clinical relevance: MD‐2 plays a protective role in HDM‐induced airway allergy with the proinflammatory regulation of airway epithelial cells and dendritic cells. MD‐2 may serve as a therapeutic target in the treatment of asthma. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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