Platelet Activating Factor And Tnf Alpha Have Synergistic Effects In Promoting Intestinal Epithelial Migration And Mucosal Wound Repair

Epithelial cells migrate and proliferate to cover denuded mucosal surfaces. The intestinal mucosal infiltrating immune cells and epithelium secrete an array of inflammatory mediators that have been proposed to modulate wound repair. Here, we report that Platelet Activating Factor (PAF), a molecule considered to be a pro-inflammatory mediator and its receptor (PAFR) are upregulated in healing colonic mucosal wounds. We show that in intestinal epithelial cells the PAFR up-regulation is downstream of TNF-α mediated signaling leading to enhanced wound repair after PAF treatment. In vitro PAF signaling promotes cell migration by activation of focal adhesion kinase that regulates dynamics of integrin containing cell-matrix contacts. On the converse, PAFR deficient mice display delayed wound closure. In addition, intraperitoneal administration of a neutralizing TNF-α antibody inhibited intestinal mucosal wound repair. Our findings highlight a cross-talk between PAFR and TNF-α in orchestrating intestinal epithelial repair.