PUBLICATION
DDX3 Participates in Translational Control of Inflammation Induced by Infections and Injuries
- Authors
- Ku, Y.C., Lai, M.H., Lo, C.C., Cheng, Y.C., Qiu, J.T., Tarn, W.Y., Lai, M.C.
- ID
- ZDB-PUB-181031-2
- Date
- 2018
- Source
- Molecular and cellular biology 39(1): (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Cytokines/metabolism
- DEAD-box RNA Helicases/immunology*
- Escherichia coli/pathogenicity
- HeLa Cells
- Humans
- Immunity, Innate/drug effects
- Immunity, Innate/immunology
- Inflammation/drug therapy
- Lipopolysaccharides/pharmacology
- Poly I-C/pharmacology
- Protein Biosynthesis/drug effects
- Protein Biosynthesis/immunology
- RNA, Messenger/drug effects
- RNA, Messenger/metabolism
- Signal Transduction/drug effects
- Signal Transduction/immunology
- Zebrafish
- PubMed
- 30373933 Full text @ Mol. Cell. Biol.
Citation
Ku, Y.C., Lai, M.H., Lo, C.C., Cheng, Y.C., Qiu, J.T., Tarn, W.Y., Lai, M.C. (2018) DDX3 Participates in Translational Control of Inflammation Induced by Infections and Injuries. Molecular and cellular biology. 39(1):.
Abstract
Recent studies have suggested that DDX3 functions in antiviral innate immunity, but the underlying mechanism remains elusive. We previously identified target mRNAs whose translation is controlled by DDX3. Pathway enrichment analysis of these targets indicated that DDX3 is involved in various infections and inflammation. Using immunoblotting, we confirmed that PACT, STAT1, GNB2, Rac1, TAK1, and p38 MAPK proteins are down-regulated by DDX3 knockdown in human monocytic THP-1 cells and epithelial HeLa cells. Polysome profiling revealed that DDX3 knockdown reduces the translational efficiency of target mRNAs. We further demonstrated DDX3-mediated translational control of target mRNAs by luciferase reporter assays. To examine the effects of DDX3 knockdown on macrophage migration and phagocytosis, we performed in vitro cell migration assay and flow cytometry analysis of the uptake of green fluorescent protein-expressing Escherichia coli in THP-1 cells. The DDX3 knockdown cells exhibited impaired macrophage migration and phagocytosis. Moreover, we used a human cytokine antibody array to identify the cytokines affected by DDX3 knockdown. Several chemokines were decreased considerably in DDX3 knockdown THP-1 cells after lipopolysaccharide or poly(I:C) stimulation. Lastly, we demonstrated that DDX3 is crucial for the recruitment of phagocytes to the site of inflammation in transgenic zebrafish.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping