The NF-κB binding site is essential for transcriptional activation of the IL-15 gene

Abstract

We cloned the 5' upstream region of IL-15 genomic DNA and examined promoter activity in macrophages stimulated with lipopolysaccharide(LPS). The 1.2 kilobase (kb) fragment of the 5' upstream region contained binding elements for LPS-inducible transcription factors such as NFIL-6 or NF-kappaB. Determined by luciferase assay following transient transfection in the J774A.1 macrophage cell line, the 1.2 kb of the 5' upstream region exhibited high promoter activity in response to LPS, while promoter activity was significantly reduced by the 5' deletion of 313 base pairs containing the NF-kappaB binding motif. Nuclear protein prepared from LPS-stimulated macrophages formed a complex with the NF-kappaB binding sequence of the IL-15 promoter. Taken together, the binding of nuclear protein to the NF-kappaB binding site is required for transcriptional activation of the IL-15 gene in LPS-stimulated macrophages.

Expression and function of wingless and frizzled homologs in rheumatoid arthritis

“…It is also well documented that activated NF B causes transcriptional activation of IL genes like IL-6, IL-8, and IL-15 (27,28). Our results showed that not only wnt5a, but also IL-6, IL-8, and IL-15, are overexpressed in cultured RA fibroblast-like synoviocytes compared with normal synovial fibroblasts.…”

“…The PKC pathway can modulate the transcription of NF Bdependent genes, which include the cytokines IL-6, IL-8, and IL-15 (25)(26)(27)(28). Indeed, the same RA synovial fibroblasts that overexpressed wnt5a also produced more IL-6, IL-8, and IL-15, compared with the normal synovial fibroblasts (Fig.…”

IL-15/IL-15Rα intracellular trafficking in human melanoma cells and signal transduction through the IL-15Rα

“…IL-15/IL-15Ra tra cking as well as modulation of IL-15Ra/TRAF2 interaction varies from cell line to cell line, this could probably cause di erent patterns of signal transduction. Since NF-kB controls the transcription of several genes such as ICAM-1 and IL-6 (Hallahan et al, 1998;Du ey et al, 1999) important in melanoma progression as well as the transcription of IL-15 (Washizu et al, 1998), these biological properties may be relevant for the acquisition of tumour escape mechanisms.…”

Altered natural killer cell differentiation in CD34+ progenitors from Chronic Myeloid Leukemia patients

“…All the patients included in this study were positive for bcr/abl, and thus the alteration of IL-15 di erentiation pathway could be an indirect consequence of the bcr/abl protein expression and its subsequent enhanced tyrosine kinase activity. In this respect, bcr/ Abl expression through NF-KB activation (Reuther et al, 1998) may be involved in IL-15 transcription (Washizu et al, 1998). It is interesting to note that bcr/abl constitute targets to the development of selective tyrosine kinase inhibitors.…”