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23 September 2018 : Animal Research  

Interleukin-33 (IL-33) Increases Hyperoxia-Induced Bronchopulmonary Dysplasia in Newborn Mice by Regulation of Inflammatory Mediators

Xiqin Tang1ABCE*

DOI: 10.12659/MSM.910851

Med Sci Monit 2018; 24: ANS6717-6728

Abstract

BACKGROUND: Interleukin-33 (IL-33) has been reported to affect chronic inflammation of the lungs, but its impact on hyperoxia-injured lungs in newborns remains obscure. This study aimed to investigate the role of IL-33 in the lungs of neonatal mice with hyperoxia-induced bronchopulmonary dysplasia (BPD).

MATERIAL AND METHODS: Twenty-four C57BL/6 baby mice were randomly separated into three groups: the on-air group (N=16); the O2 group (N=8); and the O2 + anti-IL-33 group (N=8). Forced mechanical ventilation with oxygen-rich air (MV-O2) was used in 16 mouse pups. The mouse pups were incubated in containers with either air or 85% O2 for 1, 3, 7, 14, 21, and 28 days after birth. At the end of the treatment period, the mouse lungs were studied by histology, Western blot, and quantitative real-time polymerase chain reaction (qRT-PCR) to examine the expression of the pro-inflammatory mediators, including interleukin (IL)-1β, chemokine (CC motif) ligand 1 (CXCL-1), and monocyte chemoattractant protein-1 (MCP-1).

RESULTS: Following forced MV-O2, increased levels of IL-33 in whole mouse lungs were associated with impaired alveolar growth and with changes consistent with BPD, including reduced numbers of enlarged alveoli, increased apoptosis, and increased expression of IL-1β, CXCL-1, and MCP-1. IL-33 inhibition improved alveolar development in hyperoxia-impaired lungs and suppressed IL-1β and MCP-1 expression and was associated with increased transforming growth factor-β (TGF-β) signaling, reduced pulmonary NF-κB activity and decreased expression of the TGF-β inhibitor SMAD-7 in forced MV-O2 exposed mouse pups.

CONCLUSIONS: IL-33 increased hyperoxia-induced BPD in newborn mice by regulation of the expression of inflammatory mediators.

Keywords: Bronchopulmonary Dysplasia, Hyperoxia

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750