Eph/ephrin signalling serves a bidirectional role in lipopolysaccharide-induced intestinal injury

A growing body of evidence has demonstrated that Eph/ephrin signalling may serve a central role in intestinal diseases. However, whether erythropoietin-producing hepatocellular (Eph)/ephrin signalling is associated with the development of post-infectious irritable bowel syndrome (PI-IBS) 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 protein-1, tumour necrosis factor α, interleukin (IL)-1β, IL-6, intercellular adhesion molecule 1 and vascular cell adhesion molecule-1], activated the EphA2-Ephrin A1, protein kinase B (Akt)-nuclear factor (NF)-κB, Src-NF-κB and Wnt/β-catenin signalling pathways, and inhibited EphB1-Ephrin 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 LPS-induced upregulation of proinflammatory mediators, and Akt-NF-κB, Src-NF-κB and Wnt/β-catenin signalling pathways. In addition, EphA2 mAb treatment could partially inhibit LPS-induced inactivation of EphB-Ephrin B3 signalling, while Ephrin B3 overexpression could abrogate LPS-induced activation of EphA2-Ephrin A1 signalling. EphB1/Ephrin B3 signalling may antagonise the EphA2/Ephrin A1-dependent pathway following LPS treatment. The results associated with the EphA2 signaling pathway, indicated that Eph/ephrin signalling may serve a bidirectional role in LPS-induced intestinal injury. Eph/ephrin signalling may be a novel therapeutic target for LPS-induced intestinal injury and potentially PI-IBS.