Anti-inflammatory actions of St. John's wort: inhibition of human inducible nitric-oxide synthase expression by down-regulating signal transducer and activator of transcription-1alpha (STAT-1alpha) activation
| Autor: | Ulrich Förstermann, Daniela Margotto, Hisanori Suzuki, Elisa Tedeschi, Hartmut Kleinert, Marta Menegazzi |
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| Rok vydání: | 2003 |
| Předmět: |
St. John's wort
STAT1 iNOS Anti-Inflammatory Agents Down-Regulation Gene Expression Nitric Oxide Synthase Type II Transfection chemistry.chemical_compound Tumor Cells Cultured Humans RNA Messenger Promoter Regions Genetic Transcription factor Cells Cultured Nitrites Pharmacology Janus kinase 2 biology Activator (genetics) Plant Extracts NF-kappa B Tyrosine phosphorylation DNA Interferon-Stimulated Gene Factor 3 Molecular biology Nitric oxide synthase chemistry Cell culture biology.protein STAT protein Molecular Medicine Nitric Oxide Synthase Hypericum Transcription Factors |
| Zdroj: | The Journal of pharmacology and experimental therapeutics. 307(1) |
| ISSN: | 0022-3565 |
| Popis: | St. John's wort (SJW) has been described to show anti-inflammatory properties due to its inhibitory effects on the expression of pro-inflammatory genes like cyclooxygenase-2, interleukin-6, and inducible nitric-oxide synthase (iNOS). Since iNOS plays a critical role in chronic inflammatory diseases, we have focused our attention on the regulation of iNOS expression by SJW in two different human epithelial cell lines, alveolar A549/8 and colon DLD-1 cells. SJW extract concentration dependently inhibited human iNOS expression evaluated by measuring the amounts of iNOS mRNA, iNOS protein, and NO production in both cell lines. This inhibitory effect resulted from transcriptional inhibition as shown in reporter gene experiments. With electrophoretic mobility shift experiments, we found a SJW-mediated down-regulation of the DNA binding activity of the transcription factor signal transducer and activator of transcription-1alpha (STAT-1alpha), but not of nuclear factor-kappaB. This down-regulation of the STAT-1alpha DNA binding was shown to result from reduced tyrosine phosphorylation of the STAT-1alpha protein. The diminished STAT-1alpha tyrosine phosphorylation resulted from SJW-mediated reduction of Janus kinase 2 activity. These data suggest that extracts from SJW may be a promising anti-inflammatory principle in chronic inflammatory diseases. |
| Databáze: | OpenAIRE |
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