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-1beta 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 IFNgamma/TNFalpha, neuronal IL-8 and MIP-1beta mRNA expression was significantly increased compared to control. This increase was significantly reduced by IL-1 receptor antagonist. IL-1beta-pretreated NT2-N induced the chemotaxis of PBMC, which was significantly reduced by anti-IL-8, but not by anti-MIP-1beta neutralizing antibody. Our results demonstrate that, under inflammatory conditions, neuro-epithelial interactions can modulate neuronal chemokines production through IL-1beta-dependent pathways. Furthermore, neuronal IL-1beta-induced chemotactic properties could favor the development of immune cells infiltrates within the enteric nervous system, as is observed during intestinal inflammation.
Tixier
Emmanuelle
E
Institut National de la Santé et de la Recherche Médicale U539, Hôpital Hôtel-Dieu, 44093 Nantes, France.
Galmiche
Jean-Paul
JP
Neunlist
Michel
M
D002450:Cell Communication / Q000276:immunology*; D002460:Cell Line; D018925:Chemokines / Q000276:immunology*; D004751:Enteritis / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D007155:Immunologic Factors / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology*; D015213:Neuroimmunomodulation / Q000276:immunology*; D009474:Neurons / Q000276:immunology*
D018925:Chemokines; D007155:Immunologic Factors