title: ZC3H12D attenuated inflammation responses by reducing mRNA stability of proinflammatory genes.
abstract: Infection in airspaces and lung parenchyma may cause acute lung injury and multiple organ dysfunction syndrome due to acute inflammatory response, leading to organ failure and high mortality. ZC3H12D has been shown to modulate Toll-like receptor signaling. This study aimed to investigate the change of ZC3H12D during acute lung injury and its role in inflammation processes. Mice were challenged with lipopolysaccharides (LPS) intratracheally. The expression levels of Zc3h12d, NF-κB, and cytokines were analyzed by quantitative real-time PCR (qPCR), ELISA, and Western blot. The mRNA stability was assessed by qPCR after cells were treated with actinomycin D for specified times. The 3' untranslated region (3'-UTR) of c-fos was cloned immediately downstream of the luciferase coding sequence driven by CMV promoter and luciferase activity was measured with a Luciferase Assay kit. Upon LPS treatment, ZC3H12D levels were reduced in mouse immune cells, whereas levels of NF-κB, IL-6, and TNF-α were significantly increased. Knockdown Zc3h12d in THP1 cells resulted in the upregulation of NF-κB while overexpression of Zc3h12d inhibited NF-κB expression. Ectopic Zc3h12d significantly reduced the mRNA stability of c-fos, NF-κB, TNF-α, IL-1β, and IL-6. Attachment of the c-fos 3'-UTR made luciferase expression levels sensitive to levels of ZC3H12D. The data indicated that ZC3H12D could suppress both the initial inflammation storm and chronic inflammation by targeting the mRNA of cytokines as well as NF-κB and c-fos.
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Wen-chen
authors.initials: WC
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Jia-kuan
authors.initials: JK
authors.lastname: Chen
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Zhen-dong
authors.initials: ZD
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery, Tianjin First Center Hospital, Tianjin, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Yan-ming
authors.initials: YM
authors.lastname: Xia
authors.affiliation: The College of Biology and Pharmacy, China Three Gorges University, Yichang, Hubei 443002, China.
authors.forename: Shi
authors.initials: S
authors.lastname: Lei
authors.affiliation: Department of Respiratory Medicine, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: En-qing
authors.initials: EQ
authors.lastname: Fu
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China. Electronic address: leis428@yahoo.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D055371:Acute Lung Injury / Q000235:genetics / Q000473:pathology; D000818:Animals; D018797:Cell Cycle Proteins; D015536:Down-Regulation / Q000235:genetics; D004720:Endonucleases; D004722:Endoribonucleases; D007249:Inflammation / Q000235:genetics* / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism*; D008070:Lipopolysaccharides; D008156:Luciferases / Q000378:metabolism; D008168:Lung / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D011506:Proteins / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D020871:RNA Stability / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D018797:Cell Cycle Proteins; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D011506:Proteins; D016760:Proto-Oncogene Proteins c-fos; D025521:Tumor Suppressor Proteins; D008156:Luciferases; D004720:Endonucleases; D004722:Endoribonucleases; C489862:ZC3H12D protein, human; C571148:Zc3h12d protein, mouse
keywords: Acute lung injury; Inflammation; ZC3H12D; mRNA stability