c‐Rel and p65 subunits bind to an upstream NF‐κB site in human granulocyte macrophage‐colony stimulating factor promoter involved in phorbol ester response in 5637 cells

Abstract

To further clarify the complex transcriptional regulation of the human GM-CSF gene, which was extensively investigated in activated T cells, we have studied the role of an upstream NF-KB like site in the 5637 non-lymphoid cell line, which derives from a bladder carcinoma and constitutively produces GM-CSF. This sequence, named the A element, has an active role on GM-CSF transcription and is responsive to the tumor promoter PMA in transient transfection experiments. We describe here a heterodimeric binding complex of NF-KB subunits (c-Rel and p65) which is identical to the one obtained using the HIV-LTR-KB site as recognition sequence and different from the one (c-Rel and p50) observed with nuclear extracts from Mo T-lymphoid HTLV-II infected cells.

An upstream negative regulatory element in human granulocyte‐macrophage colony‐stimulating factor promoter is recognised by AP1 family members

“…Transfections with intermediate constructs indicated a decrease of activity between pPF2000 (−2010/+26) and pPF20/pPF22 (−1742/+26; −1377/+26) and a significant increase of activity with pPF10 (−1298/+26). This confirmed that the previously described positive element between −2002 and −1984 [5, 6]was effective also in this cell type and suggested the presence of negative regulatory elements.…”

“…We previously identified a NF‐κB‐like binding site, located between −2002 and −1984, acting as a positive transcriptional element in the Mo lymphoblastoid cell line [4]. This same NF‐κB‐like binding site participates in response to phorbol ester in 5637 cells derived from bladder carcinoma [5]. These observations suggested that important regulatory elements in distal regions of the GM‐CSF promoter may significantly contribute to the transcriptional regulation of the gene, in physiological and/or pathological conditions, as well as in a tissue‐specific way.…”

Caffeic Acid Phenethyl Ester Induces Leukocyte Apoptosis, Modulates Nuclear Factor-Kappa B and Suppresses Acute Inflammation

“…NF-ÎB activation occurs in response to various nonimmune and immune stimuli, and is rapid and highly flexible. This activation has a dual function in the regulation of various immune and inflammatory processes: not only does it lead to coordinated expression of genes whose products promote inflammatory responses [4][5][6], but it also induces apoptosis of activated immune cells [3,7,8], thereby limiting the extent and duration of inflammation.…”

Molecular Regulation of Granulocyte Macrophage Colony-Stimulating Factor in Human Lung Epithelial Cells by Interleukin (IL)-1 β , IL-4, and IL-13 Involves Both Transcriptional and Post-Transcriptional Mechanisms

“…Transcription factors that bind to the CLE0 element include NF-AT, activator protein (AP)-1, surfactant protein (SP)-1, and YY-1 (5,6). A second NF-B binding site ( Ϫ 2,002 to Ϫ 1,984) is also implicated in PMA induction of the GM-CSF promoter and has been shown to bind c-Rel and p65 (7). Further, in response to T-cell receptor activation, an enhancer region, which contains functional NF-AT/AP-1 binding sites and is located 3.3 kb upstream, seems to act in conjunction with the proximal promoter (8,9).…”