ORMDL3 modulates airway epithelial cell repair in children with asthma under glucocorticoid treatment via regulating IL-33.
BACKGROUND
Study found that glucocorticoids, as first-line treatments for asthma, fails to prevent asthma recurrence. Orosomucoid-like (ORMDL) 3 is associated to childhood asthma onset and involved in the inflammation and repair of airway epithelium. We explored the functional role of ORMDL3 in glucocorticoid treatment for childhood asthma.


METHODS
Mice were sensitized with Ovalbumin (OVA) and treated with Dexamethasone (Dex), followed by OVA challenge to establish a mouse model of asthma. Histopathological changes in lung tissues were observed by hematoxylin-eosin and masson staining. Human bronchial epithelial (16HBE-14°) cells were transfected with ORMDL3 overexpression plasmid and siRNA-interleukin (IL)-33 alone or in combination, followed by Dex. Cell viability was measured by MTT assay. Cell migration was evaluated by wound healing assay. The expressions of E-cadherin and Vimentin and the activation of NF-κB and MAPK/ERK in 16HBE-14° cells were assessed by Western blot. The expressions of ORMDL3 and IL-33 in lung tissues and 16HBE-14° cells were analyzed by qRT-PCR or Western blot.


RESULTS
Dex treatment alleviated the histopathological abnormality and reversed the overexpressions of ORMDL3 and IL-33 in the lung tissues of asthmatic mice. Overexpressed ORMDL3 enhanced migration and viability, decreased E-cadherin level, increased the levels of IL-33 and Vimentin, and promoted the phosphorylation of NF-κB and MAPK/ERK in Dex-treated 16HBE-14° cells, thus reversing the effect of Dex treatment. However, siRNA-IL-33 inhibited viability and migration, increased E-cadherin level, decreased Vimentin level, and suppressed the phosphorylation of NF-κB and MAPK/ERK, thus reversing the effect of overexpressed ORMDL3 in Dex-treated 16HBE-14° cells.


CONCLUSION
ORMDL3 overexpression helped airway epithelial cellrepairin asthma via regulating IL-33 expression.
['Li|Yaqin|Y|', 'Li|Xiaoyan|X|', 'Zhou|Wenjing|W|', 'Yu|Qing|Q|', 'Lu|Yanming|Y|']
D000818:Animals D001249:Asthma D004195:Disease Models, Animal D004847:Epithelial Cells D005938:Glucocorticoids D000067596:Interleukin-33 D008168:Lung D008565:Membrane Proteins D051379:Mice D008807:Mice, Inbred BALB C D010047:Ovalbumin
ORMDL3 Airway epithelial cells Asthma Glucocorticoids IL-33