PMID- 10542212
OWN - NLM
STAT- MEDLINE
DCOM- 19991213
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 45
DP  - 1999 Nov 5
TI  - Interleukin-10 signaling blocks inhibitor of kappaB kinase activity and nuclear
      factor kappaB DNA binding.
PG  - 31868-74
AB  - The transcription factor nuclear factor kappaB (NF-kappaB) coordinates the
      activation of numerous genes in response to pathogens and proinflammatory
      cytokines and is, therefore, pivotal in the development of acute and chronic
      inflammatory diseases. In its inactive state, NF-kappaB is constitutively present
      in the cytoplasm as a p50-p65 heterodimer bound to its inhibitory protein
      IkappaB. Proinflammatory cytokines, such as tumor necrosis factor (TNF), activate
      NF-kappaB by stimulating the activity of the IkappaB kinases (IKKs) which
      phosphorylate IkappaBalpha on serine residues 32 and 36, targeting it for rapid
      degradation by the 26 S proteasome. This enables the release and nuclear
      translocation of the NF-kappaB complex and activation of gene transcription.
      Interleukin-10 (IL-10) is a pleiotropic cytokine that controls inflammatory
      processes by suppressing the production of proinflammatory cytokines which are
      known to be transcriptionally controlled by NF-kappaB. Conflicting data exists on
      the effects of IL-10 on TNF- and LPS-induced NF-kappaB activity in human
      monocytes and the molecular mechanisms involved have not been elucidated. In this
      study, we show that IL-10 functions to block NF-kappaB activity at two levels: 1)
      through the suppression of IKK activity and 2) through the inhibition of
      NF-kappaB DNA binding activity. This is the first evidence of an
      anti-inflammatory protein inhibiting IKK activity and demonstrates that IKK is a 
      logical target for blocking inflammatory diseases.
FAU - Schottelius, A J
AU  - Schottelius AJ
AD  - Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel
      Hill, North Carolina 27599-7295, USA.
FAU - Mayo, M W
AU  - Mayo MW
FAU - Sartor, R B
AU  - Sartor RB
FAU - Baldwin, A S Jr
AU  - Baldwin AS Jr
LA  - eng
GR  - AI35098/AI/NIAID NIH HHS/United States
GR  - CA75080/CA/NCI NIH HHS/United States
GR  - R01 DK 47700/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (I-kappa B Proteins)
RN  - 0 (Interleukin-8)
RN  - 0 (NF-kappa B)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 130068-27-8 (Interleukin-10)
RN  - 9007-49-2 (DNA)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.10 (CHUK protein, human)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
RN  - EC 2.7.11.10 (IKBKB protein, human)
RN  - EC 2.7.11.10 (IKBKE protein, human)
SB  - IM
MH  - Cells, Cultured
MH  - DNA/*metabolism
MH  - Humans
MH  - I-kappa B Kinase
MH  - I-kappa B Proteins/metabolism
MH  - Interleukin-10/*physiology
MH  - Interleukin-8/biosynthesis
MH  - Intestinal Mucosa/drug effects/metabolism
MH  - Monocytes/drug effects/metabolism
MH  - NF-kappa B/*metabolism
MH  - Protein-Serine-Threonine Kinases/*antagonists & inhibitors/metabolism
MH  - *Signal Transduction
MH  - Transcription, Genetic/drug effects
MH  - Tumor Necrosis Factor-alpha/pharmacology
EDAT- 1999/11/05 08:00
MHDA- 2001/03/28 10:01
CRDT- 1999/11/05 08:00
PHST- 1999/11/05 08:00 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1999/11/05 08:00 [entrez]
AID - 10.1074/jbc.274.45.31868 [doi]
AID - S0021-9258(19)51500-9 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Nov 5;274(45):31868-74. doi: 10.1074/jbc.274.45.31868.