Clinical-alimentary tractImpaired expression of peroxisome proliferator-activated receptor γ in ulcerative colitis☆
Section snippets
Transient transfections in cell lines
The colon carcinoma cell line Caco-2 (ATCC HTB-37) was used for all transient transfections and RNA expression analysis. Caco-2 cells were transfected using the FuGENE transfection reagent according to the manufacturer (Roche Diagnostics Corporation, Indianapolis, IN) and RNA was prepared after 48 hours. The luciferase assay (SDS/Promega, Madison, WI) was used according to instructions from the manufacturer. SDS/Promega describes all reporter gene constructs, the Tk-promoter-luciferase from
TLR4 can regulate peroxisome proliferator-activated receptor γ expression in colonic epithelial cells
To assess whether a TLR4-mediated signal could affect PPARγ expression, Caco-2 cells were used because this particular cell line has low baseline levels of TLR4 expression.26 The cells were stimulated with LPS for 24 hours and PPARγ expression was monitored by an RPA. As shown in Figure 1A , LPS significantly up-regulated the expression of PPARγ by approximately 3-fold compared with cells transfected with an empty vector. The up-regulation of PPARγ was observed after 24 hours and it is
Discussion
Intestinal colonic epithelial cells are an important barrier between luminal bacteria and the adaptive immune cells of the lamina propria. The epithelial lining represents a well-documented player in mucosal homeostasis. These cells secrete many mediators such as cytokines or chemokines in response to bacterial triggering, in part via the TLR4 receptor.33 As much as these cells secrete all the mediators—to promote inflammation—they may do so in their sole purpose to ensure induction of repair
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Supported by grants from IRMAD, the association F. Aupetit, syndifrais, the Centre Hospitalier et Universitaire de Lille (EA2687, CA14555, and PHRC1926), the Fondation pour la Recherche Médicale (to L. D. and P. D.); Foundation for Knowledge and Competence Development, Swedish Strategic Foundation and Cancerfonden Sweden (to E. Å. J.); the National Institutes of Health grant number HL-64322 (to S. P. and S. S. D.); INSERM, CNRS, Hôpitaux Universitaires de Strasbourg, and the European Union (GLRT-1999-00679 and GLRT-2001-00930) (to J. A.).
- 1
The authors thank C. Bisiaux for her valuable technical assistance and Marie-Christiane Moreau and Philippe Podevin who provided mice with different flora, and C3H/HeJ (Lpsd/Lpsd) and C3H/HeouJ (Lpsn/Lpsn) mice, respectively. The authors also thank Drs. Cyrus Tamboli and William J. Sandborn for critical reading of the manuscript.
- 2
L. D. and E. Å. J. contributed equally to this work.