Interleukin-33 from Monocytes Recruited to the Lung Contributes to House Dust Mite-Induced Airway Inflammation in a Mouse Model

被引:32
|
作者
Tashiro, Hiroki [1 ]
Takahashi, Koichiro [1 ]
Hayashi, Shinichiro [1 ]
Kato, Go [1 ]
Kurata, Keigo [2 ]
Kimura, Shinya [1 ]
Sueoka-Aragane, Naoko [1 ]
机构
[1] Saga Univ, Fac Med, Dept Internal Med, Div Hematol Resp Med & Oncol, Saga 840, Japan
[2] Inst Tokyo Environm Allergy, Tokyo, Japan
来源
PLOS ONE | 2016年 / 11卷 / 06期
关键词
ALVEOLAR MACROPHAGES; DENDRITIC CELLS; LYMPHOID-CELLS; SEVERE ASTHMA; IL-33; CYTOKINES; IMMUNITY; DISEASE; HETEROGENEITY; PHAGOCYTOSIS;
D O I
10.1371/journal.pone.0157571
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background Interleukin-33 (IL-33) activates group 2 innate lymphoid cells (ILC2), resulting in T-helper-2 inflammation in bronchial asthma. Airway epithelial cells were reported as sources of IL-33 during apoptosis and necrosis. However, IL-33 is known to be from sources other than airway epithelial cells such as leukocytes, and the mechanisms of IL-33 production and release are not fully understood. The aim of this study was to clarify the role of IL-33 production by monocytes in airway inflammation. Methods BALB/c mice were sensitized and challenged with a house dust mite (HDM) preparation. Airway inflammation was assessed by quantifying inflammatory cells in bronchoalveolar lavage (BAL) fluid, and IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) levels in lung. Immunohistochemistry for IL-33 in lung sections was also performed. Ly6c, CD11b, and CD11c expression was examined by flow cytometry. Clodronate liposomes were used in the HDM-airway inflammation model to deplete circulating monocytes. Results The IL-33, but not IL-25 or TSLP, level in lung homogenates was markedly increased in HDM mice compared to control mice. IL-33-positive cells in the lungs were identified using immunohistochemistry and were increased in areas surrounding bronchi and vasculature. Furthermore, IL- 33 levels were increased in mononuclear cells derived from lungs of HDM mice compared to controls. The expression of Ly6c in mononuclear cells was significantly higher in HDM mice than in controls. Treatment with clodronate liposomes led to inhibition of not only inflammatory cells in BAL fluid, airway hyper reactivity and Th2 cytokines in lung, but also IL-33 in lung. Conclusion IL-33 from monocytes recruited to the lung may contribute to the pathogenesis of HDM-induced airway inflammation.
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页数:16
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