title: The NF-κB binding site located in the proximal region of the TSLP promoter is critical for TSLP modulation in human intestinal epithelial cells.
abstract: Thymic stromal lymphopoietin (TSLP) is constitutively secreted by intestinal epithelial cells. It regulates gut DCs, therefore, contributing to the maintenance of immune tolerance. In the present report, we describe the regulation of TSLP expression in intestinal epithelial cells and characterize the role of several NF-κB binding sites present on the TSLP promoter. TSLP expression can be stimulated by different compounds through activation of p38, protein kinase A, and finally the NF-κB pathway. We describe a new NF-κB binding element located at position -0.37 kb of the promoter that is crucial for the NF-κB-dependent regulation of TSLP. We showed that mutation of this proximal NF-κB site abrogates the IL-1β-mediated transcriptional activation of human TSLP in several epithelial cell lines. We also demonstrated that both p65 and p50 subunits are able to bind this new NF-κB binding site. The present work provides new insight into epithelial cell-specific TSLP regulation.
authors: INRA, UMR 1319 MICALIS, Domaine de Vilvert, Jouy-en-Josas, France.
authors: Antonietta
authors: A
authors: Cultrone
authors: Tomas
authors: T
authors: de Wouters
authors: Omar
authors: O
authors: Lakhdari
authors: Denise
authors: D
authors: Kelly
authors: Imke
authors: I
authors: Mulder
authors: Elizabeth
authors: E
authors: Logan
authors: Nicolas
authors: N
authors: Lapaque
authors: Joel
authors: J
authors: Doré
authors: Hervé M
authors: HM
authors: Blottière
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D023061:Gene Order; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D025542:Neurofibromin 1 / Q000378:metabolism; D025581:Neurofibromin 2 / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D018808:Transcription Factor AP-1 / Q000378:metabolism; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D016328:NF-kappa B; D025542:Neurofibromin 1; D025581:Neurofibromin 2; D018808:Transcription Factor AP-1; D020928:Mitogen-Activated Protein Kinases; D000094632:Thymic Stromal Lymphopoietin