Shikonin ameliorates injury and inflammatory response of LPS‐stimulated WI‐38 cells via modulating the miR‐489‐3p/MAP2K1 axis

Pneumonia is an inflammatory disease induced by infection with different pathogens. Currently, multiple preclinical studies have revealed that shikonin, a natural naphthoquinone, can mitigate lipopolysaccharide (LPS)‐induced inflammation, but its underlying mechanism in pneumonia remains unknown. Th...

Full description

Saved in:
Bibliographic Details
Published in:Environmental toxicology 2021-09, Vol.36 (9), p.1775-1784
Main Authors: Wang, Jinchun, Chen, Zhujing, Feng, Xiaojing, Yin, Lu
Format: Article
Language:English
Subjects:
Apoptosis
Cell injury
Cell viability
Cells
Cytokines
Flow cytometry
Immunoassays
Inflammation
Inflammatory diseases
Inflammatory response
Injuries
Lipopolysaccharides
MAP2K1
MAPK pathway
miR‐489‐3p
Pathogens
Pneumonia
Regulatory mechanisms (biology)
Shikonin
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Pneumonia is an inflammatory disease induced by infection with different pathogens. Currently, multiple preclinical studies have revealed that shikonin, a natural naphthoquinone, can mitigate lipopolysaccharide (LPS)‐induced inflammation, but its underlying mechanism in pneumonia remains unknown. This research was designed to explore the function and regulatory mechanism of shikonin in LPS‐induced cell injury and inflammation in WI‐38 cells. In‐vitro model of pneumonia was constructed by treating WI‐38 cells with LPS. Expression of miR‐489‐3p and MAP2K1 was tested by RT‐qPCR and (or) Western blot analysis. Cell viability was examined by 3‐(4,5)‐dimethylthiahiazo (−z‐y1)‐3,5‐di‐phenytetrazoliumromide assay. The productions of pro‐inflammatory cytokines were determined by enzyme‐linked immunosorbent assays. Cell apoptosis was detected by Western blot and flow cytometry analysis. In the current study, LPS induced WI‐38 cell damage by inhibiting cell viability and promoting cell apoptosis and inflammation. Shikonin ameliorated LPS‐induced cell injury and elevated miR‐489‐3p expression. LPS‐induced inflammatory injury was further mitigated by upregulation of miR‐489‐3p. In addition, MAP2K1, the target of miR‐489‐3p, was upregulated by LPS. Furthermore, upregulation of MAP2K1 reversed the influence of shikonin and miR‐489‐3p mimics on LPS‐induced cell injury and inflammation. This study revealed that shikonin protected WI‐38 cells against LPS‐induced cell injury and inflammatory response by regulating the miR‐489‐3p/MAP2K1 axis, thus affecting the progression of pneumonia.
ISSN:1520-4081
1522-7278
DOI:10.1002/tox.23298