IGF2BP2­dependent STIM1 inhibition protects against LPS­induced pneumonia in vitro by alleviating endoplasmic reticulum stress and the inflammatory response.

ABSTRACT

Pneumonia is a disease caused by inflammation and has high morbidity and mortality rates. Stromal interaction molecule 1 (STIM1) is involved in the regulation of inflammatory processes. However, to the best of the authors' knowledge, the role of STIM1 in pneumonia has not yet been reported. In the present study, lipopolysaccharide (LPS) was administered to A549 cells to construct a cell damage model. The expression of STIM1 in the model cells was detected by western blotting and reverse transcription-quantitative PCR. Then, STIM1 expression was inhibited and cell survival was detected by Cell Counting Kit-8 and flow cytometry. The expression of inflammatory factors was detected by enzyme-linked immunosorbent assay and endoplasmic reticulum stress (ERS)-related proteins were detected by immunofluorescence and western blotting. Subsequently, the relationship between insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) and STIM1 was verified by RNA-binding protein immunoprecipitation assay and actinomycin D treatment. Finally, the regulatory mechanism of IGF2BP2 and STIM1 in LPS-induced A549 cells was further investigated. The results of the present study demonstrated that STIM1 expression was increased in LPS-induced A549 cells and that STIM1 knockdown inhibited LPS-induced A549 cell apoptosis and alleviated LPS-induced A549 cell inflammation and ERS. In addition, IGF2BP2 enhanced the stability of STIM1 mRNA and knockdown of IGF2BP2-regulated STIM1 expression alleviated LPS-induced ERS and inflammatory responses in A549 cells. In conclusion, knockdown of IGF2BP2-regulated STIM1 improved cell damage in the LPS-induced pneumonia cell model by alleviating ERS and the inflammatory response.