PMID- 12879265
OWN - NLM
STAT- MEDLINE
DCOM- 20040708
LR  - 20191210
IS  - 0172-8172 (Print)
IS  - 0172-8172 (Linking)
VI  - 24
IP  - 1
DP  - 2004 Jan
TI  - Interleukin-18 is regulated by G protein pathways and protein kinase signals in 
      human fibroblasts.
PG  - 1-8
AB  - Interleukin-18 (IL-18) is a member of the IL-1 cytokine family and has 
      proinflammatory activity. It has been detected in osteoarthritic (OA) and at 
      higher levels in rheumatoid arthritic (RA) synovial tissue. Therefore we 
      investigated major signal transduction pathways for their contribution to IL-18 
      expression. Here we report that cyclic adenosine monophosphate reduced and 
      ionomycin increased IL-18 mRNA in RA synovial fibroblasts (SF) but not in OA SF. 
      Moreover, activation of G-proteins by Mas-7 augmented IL-18 reverse transcriptase 
      polymerase chain reaction signals in OA SF but not in RA SF. Specific protein 
      kinase C activator phorbol myristate acetate reduced transcription and secretion 
      of IL-18 in RA SF and OA SF. Staurosporine changed spontaneous IL-18 mRNA levels 
      and increased the secretion of IL-18 protein. We conclude that G-protein 
      activation and protein kinase C activation might partially be responsible for 
      elevated IL-18 levels during RA.
FAU - Schuler, Marc K
AU  - Schuler MK
AD  - Center for Orthopedic Surgery, UKT University Hospital, Hoppe-Seyler-Strasse 3, 
      72076 Tubingen, Germany.
FAU - Aicher, Wilhelm K
AU  - Aicher WK
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20030715
PL  - Germany
TA  - Rheumatol Int
JT  - Rheumatology international
JID - 8206885
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Interleukin-18)
RN  - 0 (Mas7 protein, synthetic)
RN  - 0 (Peptides)
RN  - 0 (RNA, Messenger)
RN  - 56092-81-0 (Ionomycin)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Arthritis, Rheumatoid/immunology/metabolism/physiopathology
MH  - Cell Line, Transformed
MH  - Cells, Cultured
MH  - Cyclic AMP/metabolism/pharmacology
MH  - Enzyme Inhibitors/pharmacology
MH  - Fibroblasts/drug effects/*metabolism/ultrastructure
MH  - GTP-Binding Proteins/*metabolism
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins
MH  - Interleukin-18/*genetics/metabolism
MH  - Ionomycin/pharmacology
MH  - Microscopy, Electron, Scanning
MH  - Osteoarthritis/immunology/metabolism/physiopathology
MH  - Peptides/metabolism/pharmacology
MH  - Protein Kinase C/*metabolism
MH  - RNA, Messenger/drug effects/metabolism
MH  - Signal Transduction/drug effects/*physiology
MH  - Synovial Membrane/immunology/*metabolism/physiopathology
MH  - Tetradecanoylphorbol Acetate/pharmacology
MH  - Up-Regulation/drug effects/genetics
EDAT- 2003/07/25 05:00
MHDA- 2004/07/09 05:00
CRDT- 2003/07/25 05:00
PHST- 2002/08/31 00:00 [received]
PHST- 2003/03/03 00:00 [accepted]
PHST- 2003/07/25 05:00 [pubmed]
PHST- 2004/07/09 05:00 [medline]
PHST- 2003/07/25 05:00 [entrez]
AID - 10.1007/s00296-003-0321-4 [doi]
PST - ppublish
SO  - Rheumatol Int. 2004 Jan;24(1):1-8. doi: 10.1007/s00296-003-0321-4. Epub 2003 Jul 
      15.