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Nedd8 modification of Cullin-5 regulates lipopolysaccharide-induced acute lung injury
Zhu, Ziyan; Sun, Lei; Hao, Rui; Jiang, Hongchao; Qian, Feng; Ye, Richard D.
2017-07
Source PublicationAMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
ISSN1040-0605
Volume313Issue:1Pages:L104-L114
AbstractLung infections are major causes of acute lung injury (ALI), with limited effective treatment available. Tumor necrosis factor receptor-associated factor 6 (TRAF6) is an essential adaptor regulating Toll-like receptors (TLRs). We recently identified Cullin-5 (Cul-5) as a prominent component in the regulation of TRAF6 polyubiquitination, but its physiological significance in ALI has not been explored. In this study, we investigated the potential role of Cul-5 in regulating ALI using mice receiving intratracheal instillation of LPS. We observed that Cul-5-deficient mice displayed reduced lung injury compared with wild-type mice as evidenced by histological analysis, alveolar neutrophil infiltration, and lung liquid accumulation. In addition, inflammatory cytokine expression in bronchoal-veolar lavage fluid and lung tissue was also markedly reduced in LPS-treated Cul-5-deficient mice. Interestingly, intratracheal adoptive transfer of Cul-5(+/-) but not Cul-5(+/+) macrophages attenuated neutrophil recruitment, alveolar inflammation, and loss of barrier function in LPS-challenged wild-type mice. Finally, we demonstrated that Cul-5 neddylation following LPS exposure induced Cul-5 and TRAF6 interaction and, thereby, TFAR6 polyubiquitination, leading to NF-kappa B activation and generation of proinflammatory cytokines. Our data show that neural precursor cell expressed developmentally down-regulated protein 8 (Nedd8) modification of Cul-5 is required for its interaction with TRAF6 and activation of the TLR4-TRAF6 signaling pathway in LPS-induced ALI, a feature that may be explored for therapeutic intervention.
KeywordCullin-5 macrophage Nedd8 acute lung injury
DOI10.1152/ajplung.00410.2016
URLView the original
Indexed BySCI
Language英语
WOS Research AreaPhysiology ; Respiratory System
WOS SubjectPhysiology ; Respiratory System
WOS IDWOS:000404995100009
PublisherAMER PHYSIOLOGICAL SOC
The Source to ArticleWOS
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Cited Times [WOS]:5   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
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GB/T 7714
Zhu, Ziyan,Sun, Lei,Hao, Rui,et al. Nedd8 modification of Cullin-5 regulates lipopolysaccharide-induced acute lung injury[J]. AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY,2017,313(1):L104-L114.
APA Zhu, Ziyan,Sun, Lei,Hao, Rui,Jiang, Hongchao,Qian, Feng,&Ye, Richard D..(2017).Nedd8 modification of Cullin-5 regulates lipopolysaccharide-induced acute lung injury.AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY,313(1),L104-L114.
MLA Zhu, Ziyan,et al."Nedd8 modification of Cullin-5 regulates lipopolysaccharide-induced acute lung injury".AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY 313.1(2017):L104-L114.
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