Activation of the human RANTES gene promoter in a macrophage cell line by lipopolysaccharide is dependent on stress-activated protein kinases and the IkappaB kinase cascade: implications for exacerbation of allergic inflammation by environmental pollutants
| Autor: | Timothy S. Hiura, Stephan J. Kempiak, Andre E. Nel |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Lipopolysaccharides
Transcriptional Activation Chemokine Lipopolysaccharide Immunology IκB kinase Biology Protein Serine-Threonine Kinases Response Elements Allergic inflammation chemistry.chemical_compound Genes Reporter Hypersensitivity Immunology and Allergy Humans RNA Messenger Promoter Regions Genetic Chemokine CCL5 Messenger RNA Air Pollutants Kinase Macrophages JNK Mitogen-Activated Protein Kinases NF-kappa B Promoter Molecular biology Hydroquinones I-kappa B Kinase Transcription Factor AP-1 chemistry Calcium-Calmodulin-Dependent Protein Kinases biology.protein Signal transduction Mitogen-Activated Protein Kinases Oxidation-Reduction Protein Binding Signal Transduction |
| Zdroj: | Clinical immunology (Orlando, Fla.). 90(3) |
| ISSN: | 1521-6616 |
| Popis: | Macrophages are targeted by environmental pollutants and play a role in allergic inflammation. We explored the molecular basis for induction of RANTES (regulated upon activation, normal T-cells expressed and secreted) mRNA by lipopolysaccharide (LPS) and the redox-active quinone, tert-butylhydroxyquinone (tBHQ). We demonstrate that transcriptional activation of the human RANTES promoter by LPS is dependent on specific AP-1 and NF-kappaB response elements, which are regulated by c-Jun N-terminal kinase (JNK) and NF-kappaB kinase cascades, respectively. The transcriptional activation of the TRE3/4 site is mediated through the transcriptional activation of c-Jun by JNK. A c-Jun mutant which lacks a transcriptional activation domain interfered in the activation of the RANTES promoter. Similarly, kinase-inactive NF-kappaB inducing kinase interfered in the activation of the RANTES promoter. While activation of the RANTES promoter could also be blocked by the downstream kinase-inactive IkappaB kinases, only IKKalpha appears to be LPS-inducible. tBHQ also exerted subtle effects on the human RANTES promoter and induced mRNA expression in parallel with generating NF-kappaB shift complexes. |
| Databáze: | OpenAIRE |
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