Toll-like receptor 5- and lymphotoxin beta receptor-dependent epithelial Ccl20 expression involves the same NF-kappaB binding site but distinct NF-kappaB pathways and dynamics.
Canonical and alternative NF-kappaB pathways depend on distinct NF-kappaB members and regulate expression of different gene subset in inflammatory and steady state conditions, respectively. In intestinal epithelial cells, both pathways control the transcription of the gene coding the CCL20 chemokine. Lymphotoxin beta receptor (LTbetaR) mediates long lasting CCL20 expression whereas Toll-like receptor 5 (TLR5) signals promote inducible and transient activation. Here, we investigated whether the regulation of ccl20 expression involves different promoter sites and NF-kappaB molecules in response to TLR5 and LTbetaR stimulation. In epithelial cells, both stimulation required the same promoter regions, especially the NF-kappaB binding site but involved different NF-kappaB isoforms: p65/p50 and p52/RelB, for TLR5 and LTbetaR-dependent activation, respectively. The dynamic of activation and interaction with CCL20-specific NF-kappaB site correlated with gene transcription. Similar Ccl20 expression and NF-kappaB activation was found in the small intestine of mice stimulated with TLR5 and LTbetaR agonists. In summary, different NF-kappaB pathways modulate CCL20 transcription by operating on the same NF-kappaB binding site in the same cell type.
Sirard
Jean-Claude
JC
Institut National de la Santé et de la Recherche Médicale U801, Institut Pasteur de Lille, Université de Lille 2, Lille, France.
Didierlaurent
Arnaud
A
Cayet
Delphine
D
Sierro
Frédéric
F
Rumbo
Martin
M
D021581:Active Transport, Cell Nucleus; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D018938:Caco-2 Cells; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D054418:Chemokine CCL20 / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D005408:Flagellin / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D053259:Lymphotoxin beta Receptor / Q000819:agonists / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D015398:Signal Transduction; D051198:Toll-Like Receptor 5 / Q000378:metabolism*
C108355:CCL20 protein, human; C493447:CCL20 protein, mouse; D054418:Chemokine CCL20; D053259:Lymphotoxin beta Receptor; D016328:NF-kappa B; C495346:TLR5 protein, human; D051198:Toll-Like Receptor 5; D005408:Flagellin