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Effects of interleukin-1β on intra-amniotic lipopolysaccharide-induced alveolar arrest in neonatal rats

YANG Yi-hui1,2, LIU Cheng-bo1, CHEN Ze1, LI Wen1, ZHANG Yong-jun1   

  1. 1. Department of Neonatology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China; 2. Department of Pediatrics, Jiading District Central Hospital, Shanghai 201800, China
  • Online:2017-04-28 Published:2017-05-04

Abstract:

Objective · To investigate the effects of interleukin-1β (IL-1β) on neonatal rat alveolar arrest induced by intra-amniotic injection of lipopolysaccharide (LPS). Methods · A neonatal SD rat model of bronchopulmonary dysplasia (BPD) was constructed by intra-amniotic injection of LPS in pregnant rats. The pregnant rats (E19) were randomly assigned to Saline group, LPS group and LPS+anti-IL-1β group. The lungs of the neonatal rats were randomly collected 1, 3 and 7 days after birth. Pathological changes in the lungs were observed by hematoxylin-eosin (H-E) staining, and expression of IL-1β mRNA and protein was detected by real-time PCR and ELISA, respectively. Rat bone marrow derived primary macrophage was cultured in vitro, and given LPS intervention, then genes related with IL-1β were detected through whole transcriptome sequencing. Results · Compared with the Saline group, the alveolar counts and secondary septa counts significantly decreased, and mean liner intercept significantly increased in LPS group. Moreover, the expression of IL-1β mRNA and protein in lungs significantly increased in LPS group. The LPS-induced pathological changes of lung tissues in neonatal rats were improved by anti-IL-1β. LPS could up-regulate the expression of genes including Gbp5, Ccl3, Nod2, Ccr5, Mefv, Casp4 and Ifnar1, but down-regulate Lgals9 and Gstp1. Among these genes Gbp5, Ccl3, Nod2, Ccr5, Casp4, Ifnar1 and Lgals9 could positively regulate IL-1β production. Conclusion · LPS can induce alveolar arrest through up-regulating the expression of IL-1β in macrophages in neonatal rat BPD model. Whole transcriptome sequencing reveals that LPS can regulate the expression of IL-1β in macrophages through several paths.

Key words: interleukin-1β, macrophage, bronchopulmonary dysplasia