PMID- 10623619
OWN - NLM
STAT- MEDLINE
DCOM- 20000208
LR  - 20121115
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 267
IP  - 1
DP  - 2000 Jan 7
TI  - Parthenolide inhibits activation of signal transducers and activators of
      transcription (STATs) induced by cytokines of the IL-6 family.
PG  - 329-33
AB  - Progression of inflammatory processes correlates with the release of cell-derived
      mediators from the local site of inflammation. These mediators, including
      cytokines of the IL-1 and IL-6 families, act on host cells and exert their action
      by activating their signal transduction pathways leading to specific target gene 
      activation. Parthenolide, a sesquiterpene lactone found in many medical plants,
      is an inhibitor of IL-1-type cytokine signaling that blocks the activation of
      NF-kappaB. Here we show that parthenolide is also an effective inhibitor of
      IL-6-type cytokines. It inhibits IL-6-type cytokine-induced gene expression by
      blocking STAT3 phosphorylation on Tyr705. This prevents STAT3 dimerization
      necessary for its nuclear translocation and consequently STAT3-dependent gene
      expression. This is a new molecular mechanism of parthenolide action that
      additionally explains its anti-inflammatory activities.
CI  - Copyright 2000 Academic Press.
FAU - Sobota, R
AU  - Sobota R
AD  - Institute of Molecular Biology, Jagiellonian University, 3 Mickiewicza Avenue,
      Krakow, 31-120, Poland.
FAU - Szwed, M
AU  - Szwed M
FAU - Kasza, A
AU  - Kasza A
FAU - Bugno, M
AU  - Bugno M
FAU - Kordula, T
AU  - Kordula T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Acute-Phase Proteins)
RN  - 0 (Cytokines)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Interleukin-1)
RN  - 0 (Interleukin-6)
RN  - 0 (NF-kappa B)
RN  - 0 (OSM protein, human)
RN  - 0 (Peptides)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
RN  - 0 (Sesquiterpenes)
RN  - 0 (Trans-Activators)
RN  - 0 (alpha 1-Antichymotrypsin)
RN  - 106956-32-5 (Oncostatin M)
RN  - 2RDB26I5ZB (parthenolide)
SB  - IM
MH  - Acute-Phase Proteins/metabolism
MH  - Carcinoma, Hepatocellular
MH  - Cytokines/*pharmacology
MH  - DNA-Binding Proteins/*metabolism
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Humans
MH  - Interleukin-1/pharmacology
MH  - Interleukin-6/*pharmacology
MH  - Liver Neoplasms
MH  - NF-kappa B/antagonists & inhibitors/*metabolism
MH  - Oncostatin M
MH  - Peptides/pharmacology
MH  - Recombinant Fusion Proteins/biosynthesis
MH  - STAT3 Transcription Factor
MH  - Sesquiterpenes/*pharmacology
MH  - Signal Transduction/*drug effects/physiology
MH  - Trans-Activators/*metabolism
MH  - Transcriptional Activation
MH  - Transfection
MH  - Tumor Cells, Cultured
MH  - alpha 1-Antichymotrypsin/genetics
EDAT- 2000/01/07 00:00
MHDA- 2000/01/07 00:01
CRDT- 2000/01/07 00:00
PHST- 2000/01/07 00:00 [pubmed]
PHST- 2000/01/07 00:01 [medline]
PHST- 2000/01/07 00:00 [entrez]
AID - 10.1006/bbrc.1999.1948 [doi]
AID - S0006-291X(99)91948-4 [pii]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2000 Jan 7;267(1):329-33. doi:
      10.1006/bbrc.1999.1948.