A nuclear factor for IL-6 expression (NF-IL6) is a member of a C/EBP family.

Abstract

NF‐IL6 is a nuclear factor that specifically binds to an IL1‐responsive element in the IL‐6 gene. In this study the gene encoding NF‐IL6 has been cloned by direct screening of a lambda gt11 library using NF‐IL6 binding sequence as a ligand. The full‐length cDNA encoded a 345 amino acid protein with a potential leucine zipper structure and revealed a high degree of homology to a liver‐specific transcriptional factor, C/EBP, at the C‐terminal portion. The bacterial fusion protein bound to the CCAAT homology as well as the viral enhancer core sequences as in the case of C/EBP. Recombinant NF‐IL6 activated the human IL‐6 promoter in a sequence‐specific manner. Southern blot analysis demonstrated the high‐degree conservation of the NF‐IL6 gene through evolution and the existence of several other related genes sharing the DNA‐binding domain. NF‐IL6 mRNA was normally not expressed, but induced by the stimulation with either LPS, IL‐1 or IL‐6. Interestingly, NF‐IL6 was shown to bind to the regulatory regions for various acute‐phase protein genes and several other cytokine genes such as TNF, IL‐8 and G‐CSF, implying that NF‐IL6 has a role in regulation not only for the IL‐6 gene but also for several other genes involved in acute‐phase reaction, inflammation and hemopoiesis.

Cellular delivery of a double-stranded oligonucleotide

“…The IL-6 gene promoter contains binding sites for other transcription factors than NFkB, including AP-1, MRE and NF-IL6 transcription factors. [36][37][38][39] Both AP-1 and NF-IL6 have been shown to be involved in the regulation of IL-1b-induced IL-6 expression. 36,37,40 However, NFkB has been considered to be the predominant transcription factor regulating the IL-6 gene in response to inflammatory stimuli.…”

Models of lineage switching in hematopoietic development: a new myeloid-committed eosinophil cell line (YJ) demonstrates trilineage potential

“…The poly(A) + mRNA (4 g per lane) was denatured in formamideformaldehyde and then subjected to electrophoresis in 1% agarose-formaldehyde gels. The RNA was then transferred to Biodyne nylon membranes (Pall BioSupport, East Hills, NY, USA) and the blots probed sequentially with radiolabeled cDNAs encoding human eosinophil peroxidase (EPO), 14 human major basic protein (MBP), 15 human eosinophil cationic protein (ECP), 16 human eosinophil-derived neurotoxin (EDN), 17 human Charcot-Leyden crystal (CLC) protein, 18 neutrophil elastase, 19 gp91 phox , 20 myeloperoxidase (MPO), 21 CD14, 22 GATA-1 23 and GATA-2, 24 C/EBP␣, 25 C/EBP␤, 26 Egr-1, 27 MZF-1, 28 PU.1 29 and 18S ribosomal RNA 30 to confirm equivalent RNA loading. All hybridizations were performed with random-primed cDNA probes at 42°C for 18 h in 50% formamide, 6X SSC, 0.2% Ficoll-polyvinylpyrrolidone (PVP), and 0.1% sodium dodecyl sulfate (SDS).…”

CCAAT/ENHANCER binding protein β mediates expression of matrix metalloproteinase 13 in human articular chondrocytes in inflammatory arthritis

“…C/EBP␤ has 2 major isoforms, liverenriched activator protein (LAP) and liver-enriched inhibitory protein (LIP). LAP is generally considered to be an activator, whereas LIP, which lacks most of the transactivation domain of LAP, can act as a dominantnegative inhibitor (15,16). C/EBP␤ was first identified as a nuclear protein that bound to the IL-1 response element in the IL-6 promoter region (15).…”

“…LAP is generally considered to be an activator, whereas LIP, which lacks most of the transactivation domain of LAP, can act as a dominantnegative inhibitor (15,16). C/EBP␤ was first identified as a nuclear protein that bound to the IL-1 response element in the IL-6 promoter region (15). It is well known that C/EBP␤-deficient mice are highly susceptible to infections because of decreased macrophage activity (17).…”

“…It is well known that C/EBP␤-deficient mice are highly susceptible to infections because of decreased macrophage activity (17). C/EBP␤ binding motifs are found in the promoters of many proinflammatory genes, including IL-1␤, IL-6, IL-8, TNF␣, granulocyte colony-stimulating factor (G-CSF), nitric oxide synthase, and lysozyme (15,18). In fact, C/EBP␤ is activated by IL-1␤ or TNF␣ in cartilage and stimulates various genes related to inflammation, such as phospholipase A 2 , cyclooxygenase 2, manganese superoxide dismutase, and G-CSF (17,(19)(20)(21)(22).…”