Validation of LPS induced esophageal inflammation through TLR4 pathway in gastroesophageal reflux disease

Abstract Objective: Current researches have shown that patients with gastroesophageal reflux disease (GERD) may have esophageal microbial flora imbalance, in which Gram-negative bacteria become dominant and produce lipopolysaccharide (LPS), which can activate the Toll-like receptor 4 (TLR4) signaling pathway. Therefore, we want to validate LPS induces esophageal inflammation through TLR4 pathway in GERD. Methods: We constructed an external esophageal perfusion rat model and used normal saline, LPS and TAK-242 + LPS mixture to perfuse the middle and lower esophagus, respectively. We observed the change of esophageal tissue inner diameter, the pathological changes of the esophagus, the expression of inflammatory factors, and the content of related apoptotic proteins in different groups. Results: In LPS group, obvious inflammatory infiltration was observed. The TAK-242 + LPS group exhibited a milder inflammatory response than the LPS group. Compared with the control, the LPS group had increased inflammatory factor expression and apoptotic protein content, with lowered anti-apoptotic gene expression. TAK-242, as a TLR4 inhibitor in the TAK-242 + LPS group, effectively suppressed the LPS-stimulated inflammatory response. Conclusion: LPS exerted the powerful pro-inflammatory effect through TLR4 pathway in GERD, and TAK-242, a TLR4 inhibitor, significantly alleviated LPS-induced esophageal damage, suggesting its potential as a GERD therapy.