PMID- 11598150
OWN - NLM
STAT- MEDLINE
DCOM- 20011204
LR  - 20230216
IS  - 0023-6837 (Print)
IS  - 0023-6837 (Linking)
VI  - 81
IP  - 10
DP  - 2001 Oct
TI  - Interleukin-18 induces rheumatoid arthritis synovial fibroblast CXC chemokine 
      production through NFkappaB activation.
PG  - 1371-83
AB  - Interleukin-18 (IL-18) is a novel proinflammatory cytokine that was recently 
      found in synovial fluids and in synovial tissues from patients with rheumatoid 
      arthritis (RA). To determine the participation of IL-18 in the inflammation 
      observed in RA, we investigated the effect of IL-18 on RA synovial fibroblast 
      chemokine production. Using FACS analysis, we showed that IL-18 induced a 
      doubling in the production of intracellular IL-8 by RA synovial fibroblasts, and 
      this result was confirmed by Western blot. At the extracellular level, IL-18 
      up-regulated the secretion of IL-8 in a dose- and time-dependent manner. IL-18 
      also up-regulated the other CXC chemokines, epithelial-neutrophil activating 
      protein (ENA-78) and growth-regulated oncogene (groalpha), in a dose dependent 
      manner, but failed to induce the production of the CC chemokine, macrophage 
      inflammatory protein (MIP)-1alpha. By immunofluorescence and Western blot, we 
      demonstrated that IL-18 activates the translocation of the transcription factor 
      nuclear factor kappa B (NFkappaB) into the nucleus of RA synovial fibroblasts. 
      IL-18 induces IL-8 secretion through NFkappaB because RA synovial fibroblasts 
      pretreated with antisense to NFkappaB p65 oligonucleotide produce a mean of 44% 
      less IL-8 compared with cells pretreated with the control sense oligonucleotide. 
      These results indicate a novel role for IL-18 in inducing RA synovial fibroblast 
      expression of CXC chemokines through NFkappaB and place this cytokine in a 
      strategic role in the local inflammation observed in RA.
FAU - Morel, J C
AU  - Morel JC
AD  - Department of Medicine, Northwestern University Medical School, Chicago, IL 
      60611, USA.
FAU - Park, C C
AU  - Park CC
FAU - Kumar, P
AU  - Kumar P
FAU - Koch, A E
AU  - Koch AE
LA  - eng
GR  - AI40987/AI/NIAID NIH HHS/United States
GR  - HL58695/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
RN  - 0 (Chemokines, CXC)
RN  - 0 (Interleukin-18)
RN  - 0 (NF-kappa B)
SB  - IM
MH  - Arthritis, Rheumatoid/*metabolism/pathology
MH  - Cells, Cultured
MH  - Chemokines, CXC/*biosynthesis
MH  - Fibroblasts/metabolism
MH  - Humans
MH  - Interleukin-18/*pharmacology
MH  - NF-kappa B/metabolism
MH  - Signal Transduction/drug effects
MH  - Synovial Membrane/*metabolism/pathology
EDAT- 2001/10/13 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/10/13 10:00
PHST- 2001/10/13 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/10/13 10:00 [entrez]
AID - S0023-6837(22)03159-2 [pii]
AID - 10.1038/labinvest.3780351 [doi]
PST - ppublish
SO  - Lab Invest. 2001 Oct;81(10):1371-83. doi: 10.1038/labinvest.3780351.