The effects of Th2 cytokines on the expression of ADAM33 in allergen-induced chronic airway inflammation.
A disintegrin and metalloprotease domain 33 (ADAM33) has been identified as an asthma susceptibility gene, which is associated with small-airway remodeling. However, the role of ADAM33 in the development of allergic airway inflammation is unclear. The present study used an established murine model of allergen-induced chronic airway inflammation, which was sensitized and then challenged by nebulized 2.5% ovalbumin (OVA) for 8 weeks (30 min/day, three times a week). The expression of ADAM33 mRNA detected by real time RT-PCR was significantly enhanced in the lung tissue of mice with OVA challenge, as compared with the group challenged with saline. This OVA-challenged model showed significant Th2-biased airway inflammation as well as airway remodeling with features of sub-epithelial fibrosis and mucus hyper-secretion. Furthermore, in vitro studies showed that IL-4 and IL-13 could significantly up-regulate the expression of ADAM33 mRNA in human fibroblasts in a concentration- and time-dependent manner as compared to normal controls. These results support the note that Th2 cytokines can up-regulate the expression of ADAM33 mRNA and ADAM33 may play an important role in the development of airway remodeling in allergen-induced chronic airway inflammation.
Jie
Zhijun
Z
Department of Respiratory Medicine, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Jin
Meiling
M
Cai
Yingyun
Y
Bai
Chunxue
C
Shen
Yao
Y
Yuan
Zhenghong
Z
Hu
Yunwen
Y
Holgate
Stephen
S
D051722:ADAM Proteins / Q000378:metabolism*; D000485:Allergens; D000704:Analysis of Variance; D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005347:Fibroblasts; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism
D000485:Allergens; D016207:Cytokines; D012333:RNA, Messenger; D010047:Ovalbumin; D051722:ADAM Proteins; C499183:Adam33 protein, mouse