Aims
Growth and differentiation factor 15 (GDF15) is a stress-related factor, which implicated in various diseases. This study aimed to investigate the role of GDF15 in LPS-mediated inflammation and to explore the potential underlying molecular mechanisms in human nasal epithelial cells (HNEpCs). Main
Methods
HNEpCs were treated with LPS. GDF15 loss-of-function and gain-of-function experiments were performed. The expression of GDF15 by quantitative real-time PCR (RT-qPCR). The mRNA levels and secretion of inflammatory cytokines and MUC5AC were assessed by RT-qPCR and ELISA kits. LY294002 (PI3K inhibitor) and 740Y-P (PI3K agonist) were utilized to interfere with PI3k/Akt pathway. The relationship between GDF15 and ATF4 was identified by chromatin immunoprecipitation (ChIP) and luciferase reporter assay. Key findings: We observed that LPS triggered GDF15 expression. GDF15 ablation reduced the mRNA levels and secretion of inflammatory cytokines. GDF15 silencing led to the reduction of the MUC5AC mRNA level, protein level and secretion in response to LPS. Enhanced expression of GDF15 showed the opposite
Significance
Our data suggest that GDF15 is regulated by ATF4 and suppresses LPS-induced inflammation and MUC5AC in human nasal epithelial cells through the PI3K/Akt pathway.