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MK2 mediates macrophage activation and acute lung injury by regulating let-7e miRNA
Wu, Yaxian; He, Huiqiong; Ding, Yunhe; Liu, Sirui; Zhang, Depeng; Wang, Jun; Jiang, Hongchao; Zhang, Dan; Sun, Lei; Ye, Richard D.; Qian, Feng
2018-09
Source PublicationAMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
ISSN1040-0605
Volume315Issue:3Pages:L371-L381
AbstractMAPK-activated protein kinase 2 (MK2) plays a critical role in the development of inflammation. However, the modulatory mechanisms in macrophage activation and acute lung injury (ALI) have not been completely defined. Here, we reported that MK2-deficient mice (MK2(-/-)) protected against sepsisinduced ALI. In response to lipopolysaccharide (LPS) challenge. MK2(-/-) mice and myeloid cell-specific MK2 conditional knockout mice (MK2(Lyz2-KO)) exhibited attenuated inflammatory response, especially producing fewer amounts of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, and macrophage inflammatory protein 2 (MIP-2). LPS treatment in vitro resulted in reduced cytokine expression in MK2(-/-) bone marrow-derived macrophages (BMDMs). Furthermore. we found that LPS-induced micmRNA lethal-7e (let-7e) expression was significantly increased in MK2(-/-) macrophages. Transfection of let-7e antagomirs into MK2(-/-) BMDM rescued LPS-induced expression of TNF-alpha, IL-6, and MIP-2. In contrast. transfection of let-7e mimics into MK2'BMDM decreased cytokine expression. Meanwhile, I,PS-induced phosphorylation of cAMP response element-binding (CREB) protein, a substrate of MK2, was downregulated in MK2(-/-) BMDMs. Lin28, an inhibitory molecule of let-7, was significantly reduced in MK2(-/-) macrophages. Our results suggested that MK2 boosts LPS-induced macrophage activation and ALI via increasing activation of CREB and consequently, the expression of Lin28 and downregulation of let-7e.
Keywordacute lung injury let-7e lipopolysaccharides macrophage MAPK-activated protein kinase 2 miRNA MK2
DOI10.1152/ajplung.00019.2018
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaPhysiology ; Respiratory System
WOS SubjectPhysiology ; Respiratory System
WOS IDWOS:000443901300004
PublisherAMER PHYSIOLOGICAL SOC
The Source to ArticleWOS
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Cited Times [WOS]:20   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
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Wu, Yaxian,He, Huiqiong,Ding, Yunhe,et al. MK2 mediates macrophage activation and acute lung injury by regulating let-7e miRNA[J]. AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY,2018,315(3):L371-L381.
APA Wu, Yaxian,He, Huiqiong,Ding, Yunhe,Liu, Sirui,Zhang, Depeng,Wang, Jun,Jiang, Hongchao,Zhang, Dan,Sun, Lei,Ye, Richard D.,&Qian, Feng.(2018).MK2 mediates macrophage activation and acute lung injury by regulating let-7e miRNA.AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY,315(3),L371-L381.
MLA Wu, Yaxian,et al."MK2 mediates macrophage activation and acute lung injury by regulating let-7e miRNA".AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY 315.3(2018):L371-L381.
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