PMID- 11477102
OWN - NLM
STAT- MEDLINE
DCOM- 20011204
LR  - 20230309
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 276
IP  - 40
DP  - 2001 Oct 5
TI  - A novel role for interleukin-18 in adhesion molecule induction through NF kappa B 
      and phosphatidylinositol (PI) 3-kinase-dependent signal transduction pathways.
PG  - 37069-75
AB  - Interleukin-18 (IL-18) is a novel proinflammatory cytokine found in serum and 
      joints of patients with rheumatoid arthritis (RA). We studied a novel role for 
      IL-18 in mediating cell adhesion, a vital component of the inflammation found in 
      RA and other inflammatory diseases. We examined the expression of cellular cell 
      adhesion molecules E-selectin, vascular cell adhesion molecule-1 (VCAM-1), and 
      intercellular adhesion molecule-1 (ICAM-1) on endothelial cells and RA synovial 
      fibroblasts using flow cytometry. Adhesion of the monocyte-like cell line HL-60 
      to endothelial cells was determined by immunofluorescence. IL-18 significantly 
      enhanced ICAM-1 and VCAM-1 expression on endothelial cells and RA synovial 
      fibroblasts. In addition, IL-18 induced E-selectin expression on endothelial 
      cells and promoted the adhesion of HL-60 cells to IL-18-stimulated endothelial 
      cells. Neutralizing anti-VCAM-1 and anti-E-selectin could completely inhibit 
      HL-60 adherence to endothelial cells. IL-18-induced adhesion molecule expression 
      appears to be mediated through nuclear factor kappa B (NF kappa B) and 
      phosphatidyl-inositol 3 kinase (PI 3-kinase) since addition of inhibitors to 
      either NF kappa B (pyrrolidine dithiocarbamate and N-acetyl-l-cysteine) or PI 
      3-kinase (LY294002) inhibited RA synovial fibroblast VCAM-1 expression by 50 to 
      60%. Addition of both inhibitors resulted in inhibition of VCAM-1 expression by 
      85%. In conclusion, the ability of IL-18 to induce adhesion molecule expression 
      on endothelial cells and RA synovial fibroblasts indicates that IL-18 may 
      contribute to RA joint inflammation by enhancing the recruitment of leukocytes 
      into the joint. IL-18 requires NF kappa B as well as PI 3-kinase to induce VCAM-1 
      on RA synovial fibroblasts, suggesting that there may be two distinct pathways in 
      IL-18-induced adhesion molecule expression.
FAU - Morel, J C
AU  - Morel JC
AD  - Northwestern University Medical School, Department of Medicine, Chicago, 
      Illinois, 60611, USA.
FAU - Park, C C
AU  - Park CC
FAU - Woods, J M
AU  - Woods JM
FAU - Koch, A E
AU  - Koch AE
LA  - eng
GR  - AI-40987/AI/NIAID NIH HHS/United States
GR  - HL-58695/HL/NHLBI 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.
DEP - 20010727
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antioxidants)
RN  - 0 (E-Selectin)
RN  - 0 (Interleukin-18)
RN  - 0 (NF-kappa B)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Pyrrolidines)
RN  - 0 (Thiocarbamates)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 25769-03-3 (pyrrolidine dithiocarbamic acid)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/pharmacology
MH  - Antibodies, Monoclonal/pharmacology
MH  - Antioxidants/pharmacology
MH  - Arthritis, Rheumatoid/metabolism/pathology
MH  - Cell Adhesion/drug effects
MH  - E-Selectin/immunology/metabolism
MH  - Endothelium, Vascular/drug effects/metabolism
MH  - Fibroblasts/drug effects/metabolism
MH  - HL-60 Cells
MH  - Humans
MH  - Intercellular Adhesion Molecule-1/metabolism
MH  - Interleukin-18/*pharmacology
MH  - NF-kappa B/*physiology
MH  - Phosphatidylinositol 3-Kinases/*physiology
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Pyrrolidines/pharmacology
MH  - Signal Transduction/*physiology
MH  - Synovial Fluid/drug effects/metabolism
MH  - Thiocarbamates/pharmacology
MH  - Vascular Cell Adhesion Molecule-1/immunology/metabolism
EDAT- 2001/07/31 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/07/31 10:00
PHST- 2001/07/31 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/07/31 10:00 [entrez]
AID - S0021-9258(19)56641-8 [pii]
AID - 10.1074/jbc.M103574200 [doi]
PST - ppublish
SO  - J Biol Chem. 2001 Oct 5;276(40):37069-75. doi: 10.1074/jbc.M103574200. Epub 2001 
      Jul 27.