Interleukin-33 (IL-33) Increases Hyperoxia-Induced Bronchopulmonary Dysplasia in Newborn Mice by Regulation of Inflammatory Mediators
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China (mainland)
Med Sci Monit 2018; 24:6717-6728
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, Inflammation