The Role of IL-33 on LPS-Induced Acute Lung Injury in Mice
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ORIGINAL ARTICLE
The Role of IL-33 on LPS-Induced Acute Lung Injury in Mice Yaping Zhang,1 Ran Lv,1 Xuming Hu,1 Li Jiang,1 Dongju Xiao,1 Yv Sun,1 Jinning Zhao,1 Qi Bao,1 and Junran Xie1,2
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. IL33 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.
INTRODUCTION Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are first described in 1967 and are characterized by the abrupt onset of serious hypoxemia with diffuse alveolar damage and pulmonary infiltrates [1, 2]. ARDS is a more serious state of ALI, and both ALI and ARDS confer a severe illness burden on the individual sufferer and society [3]. Infections, particularly 1
Department of Anesthesiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 Eastern Qingchun Road, Hangzhou, 310016, People’s Republic of China 2 To whom correspondence should be addressed at Department of Anesthesiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 Eastern Qingchun Road, Hangzhou, 310016, People’s Republic of China. E-mail: [email protected]
those caused by gram-negative bacteria, are important causes of ALI and ARDS. Extracellular lipopolysaccharide (LPS) of gram-negative bacteria is the promoter of the innate immune response and inflammation, triggering inflammatory cells to pro
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