PMID- 11749970 OWN - NLM STAT- MEDLINE DCOM- 20020125 LR - 20190621 IS - 0014-5793 (Print) IS - 0014-5793 (Linking) VI - 509 IP - 3 DP - 2001 Dec 14 TI - Human macrophage inflammatory protein-3alpha/CCL20/LARC/Exodus/SCYA20 is transcriptionally upregulated by tumor necrosis factor-alpha via a non-standard NF-kappaB site. PG - 439-45 AB - The 5'-flanking sequences of the human macrophage inflammatory protein-3alpha/CCL20 gene were cloned and transfected into G-361 human melanoma cells in a luciferase reporter construct. Tumor necrosis factor-alpha (TNF-alpha) treatment stimulated luciferase expression, and promoter truncations demonstrated that TNF-alpha inducibility is conferred by a region between nt -111 and -77, which contains a non-standard nuclear factor-kappaB (NF-kappaB) binding site. The requirement for NF-kappaB was demonstrated as follows: (i) mutations in this NF-kappaB site abrogated TNF-alpha responsiveness; (ii) TNF-alpha activated a construct containing two copies of the CCL20 NF-kappaB binding site; (iii) overexpression of NF-kappaB p65 activated the CCL20 promoter; (iv) NF-kappaB from nuclear extracts of TNF-alpha-stimulated cells bound specifically to this NF-kappaB site. FAU - Harant, H AU - Harant H AD - Department of Inflammatory Diseases, Novartis Research Institute, Vienna, Austria. FAU - Eldershaw, S A AU - Eldershaw SA FAU - Lindley, I J AU - Lindley IJ LA - eng PT - Journal Article PL - England TA - FEBS Lett JT - FEBS letters JID - 0155157 RN - 0 (CCL20 protein, human) RN - 0 (CCR6 protein, human) RN - 0 (Chemokine CCL20) RN - 0 (Chemokines, CC) RN - 0 (Macrophage Inflammatory Proteins) RN - 0 (NF-kappa B) RN - 0 (Receptors, CCR6) RN - 0 (Receptors, Chemokine) RN - 0 (Transcription Factor RelA) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 1.13.12.- (Luciferases) SB - IM MH - 5' Flanking Region/genetics MH - Base Sequence MH - Cell Line MH - Chemokine CCL20 MH - Chemokines, CC/*genetics MH - Cloning, Molecular MH - Electrophoretic Mobility Shift Assay MH - Humans MH - Luciferases/genetics/metabolism MH - Macrophage Inflammatory Proteins/*genetics MH - Molecular Sequence Data MH - NF-kappa B/*metabolism MH - Promoter Regions, Genetic/genetics MH - Protein Binding MH - Receptors, CCR6 MH - *Receptors, Chemokine MH - Response Elements/*genetics MH - Transcription Factor RelA MH - Transcription, Genetic/*drug effects MH - Transcriptional Activation/*drug effects MH - Tumor Cells, Cultured MH - Tumor Necrosis Factor-alpha/*pharmacology EDAT- 2001/12/26 10:00 MHDA- 2002/01/26 10:01 CRDT- 2001/12/26 10:00 PHST- 2001/12/26 10:00 [pubmed] PHST- 2002/01/26 10:01 [medline] PHST- 2001/12/26 10:00 [entrez] AID - S0014-5793(01)03138-6 [pii] AID - 10.1016/s0014-5793(01)03138-6 [doi] PST - ppublish SO - FEBS Lett. 2001 Dec 14;509(3):439-45. doi: 10.1016/s0014-5793(01)03138-6.