PMID- 12787406
OWN - NLM
STAT- MEDLINE
DCOM- 20040319
LR  - 20191210
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 64
IP  - 1
DP  - 2003 Jul
TI  - IL-18 translational inhibition restricts IFN-gamma expression in crescentic 
      glomerulonephritis.
PG  - 160-9
AB  - BACKGROUND: Interleukin-18 (IL-18), a potent inducer of interferon gamma 
      (IFN-gamma) production, is a cytokine involved in the cell-mediated immune 
      response that is expressed during inflammatory and pathologic conditions. 
      IFN-gamma plays a role in the development of some models of glomerulonephritis 
      (GN); however, the role of IL-18 in the production of IFN-gamma during these 
      pathologies has not been studied. METHODS: Rat IL-18 cDNA was isolated and the 
      regulation of IL-18 gene expression was studied. IFN-gamma and IL-18 expression 
      were determined in anti-glomerular basement membrane (GBM) antibody (Ab)-induced 
      GN. Recombinant active IL-18 (rIL-18) was used to further identify its effect on 
      IFN-gamma production during this GN. Glomerular injury and levels of IFN-gamma 
      were assayed in Wistar Kyoto (WKY) rats with anti-GBM GN in the presence or 
      absence of rIL-18. RESULTS: Rat IL-18, similar to the mouse clone, requires 
      processing by the IL-1beta converting enzyme to become activated. A rat IL-18 
      5'-untranslated region (UTR) translational inhibitor was identified that strongly 
      inhibited the synthesis of IL-18. This translational inhibitor with different 
      lengths (180 and 130 bp) was highly expressed during GN and correlated with 
      minimal IFN-gamma mRNA expression. Injection of recombinant active IL-18 in WKY 
      rats with anti-GBM GN was associated with an increase of glomerular IFN-gamma 
      levels, proliferating cell nuclear antigen (PCNA)-ED1+ cells, and PCNA-CD8+ 
      cells, with worsening of glomerular injury. CONCLUSION: These data suggest that 
      the translational control of IL-18 expression by its 5'-UTR limits the production 
      of IL-18, resulting in restricted expression of mRNA and protein IFN-gamma in 
      this model of GN. Furthermore, it was suggested that possible IL-18/IFN-gamma 
      induction of local proliferation of macrophages and CD8+ cells might be an 
      important mechanism for amplifying CD8+-mediated macrophage-dependent GN.
FAU - Garcia, Gabriela E
AU  - Garcia GE
AD  - Department of Immunology, The Scripps Research Institute, La Jolla, California, 
      USA.
FAU - Xia, Yiyang
AU  - Xia Y
FAU - Ku, George
AU  - Ku G
FAU - Johnson, Richard J
AU  - Johnson RJ
FAU - Wilson, Curtis B
AU  - Wilson CB
FAU - Feng, Lili
AU  - Feng L
LA  - eng
GR  - DK-20043/DK/NIDDK NIH HHS/United States
GR  - DK54674-02/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  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (5' Untranslated Regions)
RN  - 0 (Interleukin-18)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Proteins)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 3.4.22.36 (Caspase 1)
SB  - IM
MH  - 5' Untranslated Regions/genetics/metabolism/physiology
MH  - Amino Acid Sequence/genetics
MH  - Animals
MH  - Anti-Glomerular Basement Membrane Disease/*metabolism/*pathology
MH  - Base Sequence/genetics
MH  - COS Cells
MH  - Caspase 1/genetics
MH  - Chlorocebus aethiops
MH  - Cloning, Molecular
MH  - Interferon-gamma/*antagonists & inhibitors/genetics
MH  - Interleukin-18/*antagonists & inhibitors/*genetics/pharmacology
MH  - Male
MH  - Molecular Sequence Data
MH  - *Protein Biosynthesis
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Inbred WKY
MH  - Recombinant Proteins/pharmacology
EDAT- 2003/06/06 05:00
MHDA- 2004/03/20 05:00
CRDT- 2003/06/06 05:00
PHST- 2003/06/06 05:00 [pubmed]
PHST- 2004/03/20 05:00 [medline]
PHST- 2003/06/06 05:00 [entrez]
AID - S0085-2538(15)49303-2 [pii]
AID - 10.1046/j.1523-1755.2003.00077.x [doi]
PST - ppublish
SO  - Kidney Int. 2003 Jul;64(1):160-9. doi: 10.1046/j.1523-1755.2003.00077.x.