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This Article Full Text Full Text (PDF) All Versions of this Article: 292/1/G231    most recent 00276.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Neunlist, M. Articles by Galmiche, J. P. Search for Related Content PubMed PubMed Citation Articles by Neunlist, M. Articles by Galmiche, J. P.

INFLAMMATION/IMMUNITY/MEDIATORS

Enteric glia inhibit intestinal epithelial cell proliferation partly through a TGF-₁-dependent pathway

¹INSERM U539, IMAD, University of Nantes, 44035 Nantes, France; ²INSERM U601, 44093 Nantes, France; ³Department of Anatomy, University of Luebeck, Luebeck, Germany; ⁴INSERM U643, 44093 Nantes, France; ⁵Technical University Munich, Department of Human Biology, Freising, Germany; ⁶Department of Gastroenterology, University of Texas Medical Branch, Galveston, Texas

Submitted 16 June 2005 ; accepted in final form 14 January 2006

Although recent studies have shown that enteric neurons control intestinal barrier function, the role of enteric glial cells (EGCs) in this control remains unknown. Therefore, our goal was to characterize the role of EGCs in the control of intestinal epithelial cell proliferation using an in vivo transgenic and an in vitro coculture model. Assessment of intestinal epithelial cell proliferation after ablation of EGCs in transgenic mice demonstrated a significant increase in crypt cell hyperplasia. Furthermore, mucosal glial network (assessed by immunohistochemical detection of S-100) is altered in colon adenocarcinoma compared with control tissue. In an in vitro coculture model of subconfluent Caco-2 cells seeded onto Transwell filters with EGCs, Caco-2 cell density and [³H]thymidine incorporation were significantly lower than in control (Caco-2 cultured alone). Flow cytometry analysis showed that EGCs had no effect on Caco-2 cell viability. EGCs induced a significant increase in Caco-2 cell surface area without any sign of cellular hypertrophy. These effects by EGCs were also seen in various transformed or nontransformed intestinal epithelial cell lines. Furthermore, TGF-₁ mRNA was expressed, and TGF-₁ was secreted by EGCs. Exogenously added TGF-₁ reproduced partly the EGC-mediated effects on cell density and surface area. In addition, EGC effects on Caco-2 cell density were significantly reduced by a neutralizing TGF- antibody. In conclusion, EGCs have profound antiproliferative effects on intestinal epithelial cells. Functional alterations in EGCs may therefore modify intestinal barrier functions and be involved in pathologies such as cancer or inflammatory bowel diseases.

colon cancer; enteric nervous system