The NF-κB Repressing Factor Is Involved in Basal Repression and Interleukin (IL)-1-induced Activation of IL-8 Transcription by Binding to a Conserved NF-κB-flanking Sequence Element

• Published in: The Journal of biological chemistry Vol. 276; no. 6; pp. 4501 - 4508
• Main Authors: Nourbakhsh, Mahtab, Kälble, Solveig, Dörrie, Anneke, Hauser, Hansjörg, Resch, Klaus, Kracht, Michael
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 09.02.2001
• Subjects: b-Interferon; Base Sequence; DNA; DNA-Binding Proteins; HeLa Cells; Humans; Interleukin-1 - physiology; Interleukin-8 - genetics; JNK Mitogen-Activated Protein Kinases; Mitogen-Activated Protein Kinases - metabolism; Molecular Sequence Data; NF-B protein; NF-kappa B - antagonists & inhibitors; NF-kappa B - metabolism; NRF protein; Protein Binding; Repressor Proteins - metabolism; Repressor Proteins - physiology; Sequence Homology, Nucleic Acid; Transcription Factors - metabolism; Transcription Factors - physiology; Transcriptional Activation
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M007532200

Interleukin (IL)-8, a prototypic chemokine, is rapidly induced by the pro-inflammatory cytokine IL-1 but is barely detectable in noninduced cells. Although there is clear evidence that the transcription factor NF-κB plays a central role in inducible IL-8 transcription, very little is known about the cis-elements and trans-acting factors involved in silencing of the IL-8 promoter. By sequence comparison with the interferon-β promoter, we found a negative regulatory element (NRE) in the IL-8 promoter overlapping partially with the NF-κB response element. Here we show that an NF-κB-repressing factor (NRF) binds to the IL-8 promoter NF-κB-NRE. Reduction of cellular NRF by expressing NRF antisense RNA results in spontaneous IL-8 gene expression. In contrast, IL-1-induced IL-8 secretion is strongly impaired by expressing NRF antisense RNA. Mutation of the NRE site results in loss of NRF binding and increased basal IL-8 transcription. On the other hand IL-1-induced IL-8 transcription is decreased by mutating the NRE. These data provide evidence for a dual role of the NRF in IL-8 transcription. Although in the absence of stimulation it is involved in transcriptional silencing, in IL-1-induced cells it is required for full induction of the IL-8 promoter.