Interleukin 16 (IL-16) is a chemoattractant cytokine with various effects on cellular activities and diseases. Inflammatory bowel disease (IBD) has long been a worldwide health care problem. Although its clinical features have been well described, its etiology and pathogenesis remains unclear. Moreover, the involvement of IL-16 in IBD is still far from comprehension. Here, we report for the first time, the mechanism by which IL-16 induces intestinal inflammation by up-regulating the expression of oligopeptide transporter member 1 (PepT1) in a Tetraodon nigroviridis fish model. A dextran sulfate sodium (DSS)-induced IBD model in this species revealed that the IL-16 level significantly increased accompanied by the elevation of PepT1 in the colon. Moreover, the signs of IBD were dramatically attenuated by IL-16 depletion using anti-IL-16 antibodies. In vivo administration of IL-16 induces remarkable intestinal inflammation with typical IBD features, including a series of histological damages, increased MPO activity and pro-inflammatory cytokines expression, which corresponds with significant PepT1 upregulation in the colon. Our study provides the first evidence of the connection between IL-16 and PepT1, which provides new insights into the molecular mechanism underlying IBD development. We hope that this study would provide a better understanding of IL-16 biology from fish to mammals, and the development of IL-16-based therapies for IBD.
- Copyright © 2013 by The American Association of Immunologists, Inc.