RT Journal Article
SR Electronic
T1 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-1α (STAT-1α) Activation
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 254
OP 261
DO 10.1124/jpet.103.054460
VO 307
IS 1
A1 Tedeschi, Elisa
A1 Menegazzi, Marta
A1 Margotto, Daniela
A1 Suzuki, Hisanori
A1 Förstermann, Ulrich
A1 Kleinert, Hartmut
YR 2003
UL http://jpet.aspetjournals.org/content/307/1/254.abstract
AB 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-1α (STAT-1α), but not of nuclear factor-κB. This down-regulation of the STAT-1α DNA binding was shown to result from reduced tyrosine phosphorylation of the STAT-1α protein. The diminished STAT-1α 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. The American Society for Pharmacology and Experimental Therapeutics