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Characterization of the Promoter for the Human Long Pentraxin PTX3

A. Basile,A. Sica,E. d’Aniello,F. Breviario,G. Garrido,M. Castellano,A. Mantovani,M. Introna

Published 1997 in Journal of Biological Chemistry

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-α (TNFα) and interleukin (IL)-1β 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-1β and TNFα responsiveness is not seen in the Hep 3B hepatoma cell line. The minimal promoter contains one NF-κB 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-κB proteins and to respond to TNFα and IL-1β in functional assays. Sp1- and AP-1 binding sites lying in proximity to the NF-κB 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-κB site.

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