Sinomenine attenuates lipopolysaccharide-induced inflammation and apoptosis of WI-38 cells by reducing glutathione S-transferase M1 expression.

Abstract

Pediatric pneumonia is an infectious lung disease with high morbidity and mortality. Sinomenine, an alkaloid extracted from Caulis Sinomenii, exerts anti-inflammatory and anti-apoptotic activities. Lipopolysaccharide (LPS) is widely used for the establishment of an inflammatory model. This research aimed to explore the influences of sinomenine on LPS-caused inflammatory injuries in fetal lung WI-38 cells. WI-38 cells were treated with LPS to establish a cellular model of pediatric pneumonia. Cell viability was evaluated using CCK-8 assay. Apoptosis was evaluated using TUNEL staining and caspase-3 activity assays. Inflammatory cytokines and NF-κB p65 phosphorylation levels were measured by Enzyme-Linked Immunosorbent Assay. Glutathione S-transferase M1 (GSTM1) expression was detected by western blotting. Results showed that LPS reduced WI-38 cell viability, and sinomenine protected cells against LPS-induced viability reduction. Sinomenine concentration-dependently attenuated LPS-induced inflammation by reducing TNF-α, IL-1β and MCP-1, and increasing IL-10 levels. Sinomenine mitigated LPS-induced apoptosis. GSTM1 was screened by matching the targets of sinomenine and pediatric pneumonia. GSTM1 was upregulated in LPS-treated WI-38 cells, and this effect was attenuated after sinomenine treatment. GSTM1 was upstream of NF-κB pathway. Overexpression of GSTM1 reversed the suppressive functions of sinomenine on LPS-stimulated inflammation and apoptosis. Overall, sinomenine attenuates inflammation and apoptosis in WI-38 cells stimulated by LPS via inhibiting GSTM1 expression, indicating the therapeutic potential of sinomenine in pediatric pneumonia.