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

Abstract

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.

Long noncoding RNA TPTEP1 suppresses diabetic retinopathy by reducing oxidative stress and targeting the miR-489-3p/NRF2 axis

“…Overexpression of TPTEP1 inhibited the viability and proliferation of HRVECs, and suppressed oxidative stress, suggesting that TPTEP1 could be a potential target for DR. Additionally, further study showed that TPTEP1 could directly target miR-489-3p. MiR-489-3p is related to the regulation of gastric cancer (Mao et al, 2021) and inflammatory response (Wang et al, 2021;Ye et al, 2021). However, miR-489-3p is rarely studied in the development of DR/The reports on the roles of miR-489-3p in DR are limited.…”

Apigenin attenuates inflammatory response in allergic rhinitis mice by inhibiting the TLR4/MyD88/NF‐κB signaling pathway

“…LPS was reported to be used in the induction of inflammatory responses in a variety of human cells. [33][34][35] We used LPS to induce mast cell inflammatory responses. Our data showed that apigenin suppressed the LPS-induced decrease in cell viability and increase in cell apoptosis and the levels of inflammatory factors (including IL-6, TNF-α, and IL-1β).…”

“…Here, we found that apigenin treatment blocked the production of β‐hexosaminidase and histamine induced by compound 48/80 in mast cells. LPS was reported to be used in the induction of inflammatory responses in a variety of human cells 33–35 . We used LPS to induce mast cell inflammatory responses.…”

JMJD3 downregulates IL4i1 aggravating lipopolysaccharide‐induced acute lung injury via H3K27 and H3K4 demethylation

“…24 LPS is a vital constituent of the endotoxin secreted by gram-negative bacilli and is the leading cause of ALI. 20,25 Epigenetic modifications are involved in macrophage activation and differentiation. 26 Our results suggested that LPS-induced Macrophage is a central mediator in LPS-induced inflammatory response, both in the promotion and resolution of inflammation 27 via its dominant M1 or M2 phenotype in ALI.…”

“…ALI is characterized by the infiltration of excessive inflammatory cells 24 . LPS is a vital constituent of the endotoxin secreted by gram‐negative bacilli and is the leading cause of ALI 20,25 . Epigenetic modifications are involved in macrophage activation and differentiation 26 .…”