Eph/ephrin signalling serves a bidirectional role in lipopolysaccharide­induced intestinal injury.

A growing body of evidence has demonstrated that Eph/ephrin signalling may serve a central role in intestinal diseases. However, whether erythropoietin­producing hepatocellular (Eph)/ephrin signalling is associated with the development of post­infectious irritable bowel syndrome (PI­IBS) is still unknown. In the present study, the role of Eph/Ephrin signalling in lipopolysaccharide (LPS)­induced intestinal injury was evaluated in vivo and in vitro. LPS treatment significantly increased the levels of proinflammatory mediators [monocyte chemoattractant protein­1, tumour necrosis factor α, interleukin (IL)­1ß, IL­6, intercellular adhesion molecule 1 and vascular cell adhesion molecule­1], activated the EphA2­Ephrin A1, protein kinase B (Akt)­nuclear factor (NF)­κB, Src­NF­κB and Wnt/ß­catenin signalling pathways, and inhibited EphB1­Ephrin B3 signalling in colon tissues, and primary cultured enteric neuronal and glial cells. Notably, EphA2 monoclonal antibody (mAb) treatment or Ephrin B3 overexpression could partially alleviate the LPS­induced upregulation of proinflammatory mediators, and Akt­NF­κB, Src­NF­κB and Wnt/ß­catenin signalling pathways. In addition, EphA2 mAb treatment could partially inhibit LPS­induced inactivation of EphB­Ephrin B3 signalling, while Ephrin B3 overexpression could abrogate LPS­induced activation of EphA2­Ephrin A1 signalling. EphB1/Ephrin B3 signalling may antagonise the EphA2/Ephrin A1­dependent pathway following LPS treatment. The results associated with the EphA2 signaling pathway, indicated that Eph/ephrin signalling may serve a bidirectional role in LPS­induced intestinal injury. Eph/ephrin signalling may be a novel therapeutic target for LPS­induced intestinal injury and potentially PI­IBS.