title: Characterization of the promoter for the human long pentraxin PTX3. Role of NF-kappaB in tumor necrosis factor-alpha and interleukin-1beta regulation.
abstract: The "long pentraxins" are an emerging family of genes that have conserved in their carboxy-terminal halves a pentraxin domain homologous to the prototypical acute phase protein pentraxins (C-reactive protein and serum amyloid P component) and acquired novel amino-terminal domains. In this report, a genomic fragment of 1371 nucleotides from the human "long pentraxin" gene PTX3 is characterized as a promoter on tumor necrosis factor-alpha (TNFalpha) and interleukin (IL)-1beta exposure in transfected 8387 human fibroblasts by chloramphenicol acetyltransferase and RNase protection assays. In the same cells, the PTX3 promoter does not respond to IL-6 stimulation. Furthermore, IL-1beta and TNFalpha responsiveness is not seen in the Hep 3B hepatoma cell line. The minimal promoter contains one NF-kappaB element which is shown to be necessary for induction and able to bind p50 homodimers and p65 heterodimers but not c-Rel. Mutants in this site lose the ability to bind NF-kappaB proteins and to respond to TNFalpha and IL-1beta in functional assays. Sp1- and AP-1 binding sites lying in proximity to the NF-kappaB site do not seem to play a major role for cytokine responsiveness. Finally, cotransfection experiments with expression vectors validate that the natural promoter contains a functional NF-kappaB site.
authors.affiliation: Istituto di Ricerche Farmacologiche "Mario Negri," via Eritrea, 62, 20157 Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Basile
authors.forename: A
authors.initials: A
authors.lastname: Sica
authors.forename: E
authors.initials: E
authors.lastname: d'Aniello
authors.forename: F
authors.initials: F
authors.lastname: Breviario
authors.forename: G
authors.initials: G
authors.lastname: Garrido
authors.forename: M
authors.initials: M
authors.lastname: Castellano
authors.forename: A
authors.initials: A
authors.lastname: Mantovani
authors.forename: M
authors.initials: M
authors.lastname: Introna
mesh_terms: D000818:Animals; D001483:Base Sequence; D002097:C-Reactive Protein / Q000235:genetics* / Q000378:metabolism; D003001:Cloning, Molecular; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012260:Ribonucleases / Q000378:metabolism; D016415:Sequence Alignment; D017384:Sequence Deletion; D000683:Serum Amyloid P-Component / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D000099153:Pentraxins
chemical_list: D002097:C-Reactive Protein; D007375:Interleukin-1; D016328:NF-kappa B; D012260:Ribonucleases; D000683:Serum Amyloid P-Component; D014409:Tumor Necrosis Factor-alpha; D000099153:Pentraxins