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Inflammation

, Volume 40, Issue 1, pp 285–294 | Cite as

The Role of IL-33 on LPS-Induced Acute Lung Injury in Mice

  • Yaping Zhang
  • Ran Lv
  • Xuming Hu
  • Li Jiang
  • Dongju Xiao
  • Yv Sun
  • Jinning Zhao
  • Qi Bao
  • Junran XieEmail author
ORIGINAL ARTICLE

Abstract

The objective of the study is to investigate the role and specific molecular mechanism of interleukin-33 (IL-33) acted on acute lung injury (ALI) induced by lipopolysaccharide (LPS). C57BL/6 mice intratracheally instilled LPS to induce ALI model. The mice were randomly divided into three groups: the sham operation group (Sham), ALI group (ALI), and pretreatment with IL-33 of ALI group (IL-33). By observing the survival rate, inflammatory cytokines in bronchoalveolar lavage fluid (BALF), myeloperoxidase (MPO) levels in lung tissue, lung histopathological examination, pulmonary capillary leakage, lung wet/dry (W/D) weight ratio, fibrosis levels in lung tissue, and associated pathways changes among the different groups, comparing to explore the role of IL-33 pretreatment on ALI mice and the possible molecular mechanisms. IL-33 pretreatment overall decreased the survival rate of ALI mice. IL-33 aggravated inflammation reaction showing as increasing the release of proinflammatory cytokines TNF-α and IL-6, increasing MPO levels in lung tissue, and aggravating lung pathology injury. In addition, IL-33 pretreatment further destroyed adherens junctions (AJs) by increasing the phosphorylation of VE-cadherin, resulting in the concomitantly pulmonary capillary barrier damage and pulmonary edema. During this process, mitogen-activated protein kinase (MAPK) pathways further activated. However, IL-33 pretreatment had no significant impact on collagen content of lung tissue. Our results indicated that IL-33 aggravated inflammatory reaction and increased microvascular permeability, but had little effect on pulmonary fibrosis, associated with the further activation of MAPK family proteins in the process. To sum up, IL-33 decreased survival rate and aggravated LPS-induced ALI.

KEY WORDS

IL-33 ALI MAPK 

Notes

Acknowledgements

This study was supported by grants from the National Natural Science Foundation of China (81171639) and Provincial Natural Science Foundation of Zhejiang (LQ16H150001).

Authors’ Contributions

Junran Xie and Ran Lv conceived and designed the experiments and supervised the project. Yaping Zhang performed experiments and interpreted the data. All the authors participated in manuscript writing and approved the final manuscript.

Compliance with Ethical Standards

Conflict of Interest

The authors declare they have no conflict of interest.

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Yaping Zhang
    • 1
  • Ran Lv
    • 1
  • Xuming Hu
    • 1
  • Li Jiang
    • 1
  • Dongju Xiao
    • 1
  • Yv Sun
    • 1
  • Jinning Zhao
    • 1
  • Qi Bao
    • 1
  • Junran Xie
    • 1
    Email author
  1. 1.Department of Anesthesiology, Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhouPeople’s Republic of China

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