Molecular Mechanism of Biofilm Locator Protein Kinase Dbf2p-related kinase 1 in Regulating Innate Immune Response to Interleukin 17-induced Viral Pneumonia.

Abstract

It focused on the antiviral immune regulation of biofilm-localized protein kinase Dbf2p-related kinase 1 (NDR1) in viral pneumonia. Mouse alveolar monocyte RAW264.7 was used as blank control, and viral pneumonia cell model was prepared by infecting cells with respiratory syncytial virus (RSV). NDR1 overexpression vector and siRNA interference sequences were synthesized, and overexpression/silence NDR1 cell model was fabricated. About 50 ng/mL interleukin 17 (IL-17) was given to stimulate. Enzyme-linked immunosorbent assay (ELISA), quantitative reverse transcription PCR (RT-qRCR), and Western blot were performed to detect cytokines and chemokines, mRNA of inflammatory factors, and signal molecule protein expression. Notably, RSV infection increased RSV-F mRNA in RAW264.7 cells and reduced NDR1 mRNA and protein. Secretion levels of IL-6, interferon β (IFN-β), chemokine (C-X-C motif) ligand 2 (CXCL2), and chemokine (C-C motif) ligand 2 (CCL20) increased in the model group versus blank control (P< 0.05). IL-6, IFN-β, tumor necrosis factor α (TNF-α), and toll-like receptor 3 (TLR3) mRNA were up-regulated (P < 0.05). Extracellular signal-regulated kinase (ERK1/2), p38 protein phosphorylation, human recombinant 1 (TBK1), and nuclear factor kappa-B (NF-κB) protein levels increased (P < 0.05). After overexpression of NDR1, the secretion levels of cytokines and chemokines, inflammatory factors mRNA, and signal molecule protein increased significantly. After NDR1 was silenced, cytokines and chemokines, inflammatory factors mRNA, and signal molecule protein were not significantly different versus blank control group (P > 0.05). In short, NDR1 regulated innate immune response to viral pneumonia induced by IL-17, which can be used as a new target for the treatment of IL-17-induced inflammatory response and autoimmune diseases.

• Authors: Haifeng Wang, Lina Bu, Fang Shu, Yun Bai, Feixiao Xue, Shanshan Shi, Daqing Sun
• Journal: Bioengineered (Bioengineered) Vol. 12 Issue 2 Pg. 10335-10344 (12 2021) ISSN: 2165-5987 [Electronic] United States
• PMID: 34699306 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chemokines
• Interleukin-17
• NDR1 protein kinase, mouse
• Protein Serine-Threonine Kinases

Topics

• Animals
• Biofilms (growth & development)
• Cell Proliferation
• Chemokines (metabolism)
• Immunity, Innate
• Inflammation (pathology)
• Interleukin-17 (metabolism)
• Mice
• Pneumonia, Viral (enzymology, immunology)
• Protein Serine-Threonine Kinases
• RAW 264.7 Cells
• Respiratory Syncytial Virus Infections (immunology, virology)
• Respiratory Syncytial Viruses (physiology)
• Signal Transduction