Intestinal neuro-epithelial interactions modulate neuronal chemokines production ☆

Human enteric neurons have recently been shown to produce chemokines during intestinal inflammation. However, whether (1) neuro-epithelial interactions modulate neuronal chemokines production and (2) neurons can induce the chemotaxis of immune cells remain unknown. Neuro-epithelial interactions were studied using a coculture model composed of human neurons (NT2-N) and intestinal epithelial cells (Caco-2). IL-8 or MIP-1β expression was analyzed by quantitative-PCR, ELISA or immunohistochemistry. Neuronally induced chemotaxis was studied using a coculture model composed of NT2-N and human peripheral blood mononuclear cells (PBMC). Following Caco-2 inflammation with IFNγ/TNFα, neuronal IL-8 and MIP-1β mRNA expression was significantly increased compared to control. This increase was significantly reduced by IL-1 receptor antagonist. IL-1β-pretreated NT2-N induced the chemotaxis of PBMC, which was significantly reduced by anti-IL-8, but not by anti-MIP-1β neutralizing antibody. Our results demonstrate that, under inflammatory conditions, neuro-epithelial interactions can modulate neuronal chemokines production through IL-1β-dependent pathways. Furthermore, neuronal IL-1β-induced chemotactic properties could favor the development of immune cells infiltrates within the enteric nervous system, as is observed during intestinal inflammation.