Over-expression of IL-33 leads to spontaneous pulmonary inflammation in mIL-33 transgenic mice.
IL-33 plays an important role in inflammatory diseases including hypersensitive diseases like asthma, autoimmune diseases like rheumatoid arthritis, cardiovascular diseases like heart failure and neurodegenerative diseases like Alzheimer's disease. Here we reported the generation of an IL-33 transgenic mouse, in which mouse IL-33 full-length cDNA was controlled under the CMV promoter. The transgenic IL-33 was released as a cleaved form with molecular weight of 18kDa in pulmonary, nephritic, cardiac and pancreatic tissues in transgenic mice and the pI of 18kDa peptide was about pH 3-5 on the 2D PAGE which was similar with the activated peptide of IL-33. Histological analysis showed massive airway inflammation with infiltration of eosinophils around bronchi and small blood vessels, hyperplasia of goblet cells and accumulation of mucus-like material in pulmonary tissue of transgenic mice. An increase of IL-5, IL-8, IL-13 and IgE was detected in bronchoalveolar lavage fluid (BALF) of transgenic mice, which are inflammatory factors. These findings suggest transgenic IL-33 could be cleaved and secreted in an activated form and play an important role in the pathogenesis of pulmonary inflammation.
Zhiguang
Xiang
X
Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Institute of Laboratory Animal Science, Peking Union Medical College/Chinese Academy of Medical Science, Beijing 100021, China.
Wei
Chen
C
Steven
Ravary
R
Wei
Dong
D
Wei
Zhang
Z
Rong
Mu
M
Zhanguo
Li
L
Lianfeng
Zhang
Z
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002465:Cell Movement / Q000235:genetics; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004804:Eosinophils / Q000473:pathology; D020397:Goblet Cells / Q000473:pathology; D006965:Hyperplasia; D018836:Inflammation Mediators / Q000378:metabolism; D000067596:Interleukin-33; D007378:Interleukins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009079:Mucociliary Clearance / Q000235:genetics / Q000276:immunology; D011014:Pneumonia / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D019076:Transgenes / Q000235:genetics / Q000276:immunology
D016207:Cytokines; C506535:Il33 protein, mouse; D018836:Inflammation Mediators; D000067596:Interleukin-33; D007378:Interleukins