Curcumin alleviates LPS-induced WI-38 cell inflammation injury by regulating PTGS2 expression.

Abstract

Background: Infantile pneumonia is a common infectious disease affecting infants and young children, which can lead to severe complications such as heart failure, significantly increasing morbidity and mortality rates among affected populations. Curcumin (CUR), a prominent natural polyphenol found in turmeric and other species of Curcuma, exhibits anti-inflammatory, antioxidant, and anticancer properties. Consequently, CUR has been hoped to be a therapeutic or preventive agent for several main human diseases. This study aims to explore the effects of CUR on lipopolysaccharide (LPS)-treated Wistsar Institute (WI)-38 cells.

Methods: The cell vitality, proliferation, and apoptosis were assessed by cell counting kit-8 (CCK8) assay, 5-ethynyl-2'-deoxyuridine (EdU), and flow cytometry assays. Inflammation and oxidative stress were examined by measuring interleukins (IL)-6, IL-1β, tumor necrosis factor α (TNF-α), malondialdehyde (MDA), and superoxide dismutase (SOD) levels using the corresponding enzyme-linked immunosorbent assay (ELISA) test kits. The network pharmacology and molecule docking were carried out to predict the critical targets and potential therapeutic mechanisms of CUR in infantile pneumonia. The key target genes were predicted using PPI in the CUR protected-infantile pneumonia effect. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were employed to exhibit the biological function. The results of prediction were confirmed in vitro experiments.

Results: LPS inhibited the vitality, proliferation, and SOD levels of WI-38 cells and facilitated the cell apoptosis, IL-6, IL-1β, TNF-α, and MDA levels. CUR abolished LPS-induced regulation WI-38 cell biological functions. Besides, the 16 hub genes from potential target genes of CUR and infantile pneumonia were screened. Moreover, six hub genes (enhanced green fluorescent protein (EGFP), v-akt murine thymoma viral oncogene homolog 1 (AKT1), prostaglandin endoperoxide synthase (PTGS2), signal transducer and activator of transcription 3 (STAT3), matrix metalloproteinase 9 (MMP9), and tumor necrosis factor (TNF)) in the CUR-protected-infantile pneumonia effect were identified by PPI analysis. The therapeutic effects of CUR on infantile pneumonia might relate to anti-viral and anti-inflammatory effects predicted by GO and KEGG enrichment analysis. Interestingly, CUR repressed LPS-stimulated facilitation of PTGS2 expression. The molecular docking demonstrated that PTGS2 could directly bind to CUR. The PTGS2 levels were inhibited by CUR treatment and negatively related to the time after WI-38 cells were treated with cycloheximide (CHX). PTGS2 knockdown could promote LPS-induced injury in WI-38 cells. CUR expedited cell vitality and proliferation and suppressed cell apoptosis, inflammation, and oxidative stress in LPS-induced WI-38 cells via down-regulating PTGS2.

Conclusion: CUR attenuates LPS-induced WI-38 cell injury by downregulating PTGS2. CUR may be the potential drug for alleviating LPS-induced WI-38 cell inflammation damage via regulating PTGS2 expression.