Epigallocatechin-3-gallate ameliorates lipopolysaccharide-induced inflammation via the 67LR/JAK2/STAT3 signaling pathway

Lipopolysaccharide (LPS) can trigger an inflammatory response in lung epithelial cells, which may contribute to the development of Acute Respiratory Distress Syndrome (ARDS). Epigallocatechin-3- gallate (EGCG), a bioactive constituent in green tea, is widely acknowledged for its anti-inflammatory characteristics. This study explored the anti-inflammatory effects of EGCG and its potential molecular mechanisms in mouse lung epithelial-12 (MLE-12) cells. MLE-12 cells were pre-exposed to increasing EGCG concentrations (5, 7.5, and 10 µM) for 24 h, followed by exposure to LPS (20 ng/mL) to induce inflammation After induction, cell and supernatant samples were collected. A range of detection methods were applied to systematically assess the anti-inflammatory activities and the latent mechanisms of EGCG, comprising real-time polymerase chain reaction assay (RT-PCR), enzyme-linked immunosorbent assays (ELISA), western blotting, the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), transcriptome Sequencing, immunofluorescence, co-immunoprecipitation, and confocal microscopy imaging. EGCG exhibited anti-inflammatory effects in LPS-stimulated MLE-12 cells by inhibiting the pro-inflammatory cytokines IL-1β, IL-6, and TNF-α. Its primary mechanism involves robust attachment to 67-kDa laminin receptor (67LR), which modulates the interaction between 67LR and the JAK2 protein within the JAK2/STAT3 signaling pathway. This results in a considerable diminishment in LPS-induced production and expression of inflammatory-promoting cytokines in MLE-12 cells. EGCG attenuates the inflammatory reaction in MLE-12 cells by binding to 67LR and inhibiting the JAK2/STAT3 signaling pathway. The current study explored the effects of EGCG on LPS-induced inflammation in MLE-12 cells, which may offer some new perspectives in inflammation research and broadening our comprehension of the fundamental mechanisms inflammation-related diseases. Considering EGCG's role in suppressing inflammation in MLE-12 cells, it is reasonable to advocate, from a preventive perspective, the inclusion of EGCG-rich foods as a dietary component for helping alleviate the probability of inflammation-associated disorders.

67-kDa laminin receptor; Acute respiratory distress syndrome; Epigallocatechin-3-gallate; Inflammatory; JAK2/STAT3 signaling pathway.