PMID- 15743487
OWN - NLM
STAT- MEDLINE
DCOM- 20051215
LR  - 20181113
IS  - 1478-6362 (Electronic)
IS  - 1478-6354 (Print)
IS  - 1478-6354 (Linking)
VI  - 7
IP  - 2
DP  - 2005
TI  - Local IL-13 gene transfer prior to immune-complex arthritis inhibits chondrocyte 
      death and matrix-metalloproteinase-mediated cartilage matrix degradation despite 
      enhanced joint inflammation.
PG  - R392-401
AB  - During immune-complex-mediated arthritis (ICA), severe cartilage destruction is 
      mediated by Fcgamma receptors (FcgammaRs) (mainly FcgammaRI), cytokines (e.g. 
      IL-1), and enzymes (matrix metalloproteinases (MMPs)). IL-13, a T helper 2 (Th2) 
      cytokine abundantly found in synovial fluid of patients with rheumatoid 
      arthritis, has been shown to reduce joint inflammation and bone destruction 
      during experimental arthritis. However, the effect on severe cartilage 
      destruction has not been studied in detail. We have now investigated the role of 
      IL-13 in chondrocyte death and MMP-mediated cartilage damage during ICA. IL-13 
      was locally overexpressed in knee joints after injection of an adenovirus 
      encoding IL-13 (AxCAhIL-13), 1 day before the onset of arthritis; injection of 
      AxCANI (an empty adenoviral construct) was used as a control. IL-13 significantly 
      increased the amount of inflammatory cells in the synovial lining and the joint 
      cavity, by 30% to 60% at day 3 after the onset of ICA. Despite the enhanced 
      inflammatory response, chondrocyte death was diminished by two-thirds at days 3 
      and 7. The mRNA level of FcgammaRI, a receptor shown to be crucial in the 
      induction of chondrocyte death, was significantly down-regulated in synovium. 
      Furthermore, MMP-mediated cartilage damage, measured as neoepitope (VDIPEN) 
      expression using immunolocalization, was halved. In contrast, mRNA levels of 
      MMP-3, -9, -12, and -13 were significantly higher and IL-1 protein, which induces 
      production of latent MMPs, was increased fivefold by IL-13. This study 
      demonstrates that IL-13 overexpression during ICA diminished both chondrocyte 
      death and MMP-mediated VDIPEN expression, even though joint inflammation was 
      enhanced.
FAU - Nabbe, Karin C A M
AU  - Nabbe KC
AD  - Department of Experimental Rheumatology and Advanced Therapeutics, University 
      Medical Center Nijmegen, Nijmegen, The Netherlands. k.nabbe@reuma.umcn.nl
FAU - van Lent, Peter L E M
AU  - van Lent PL
FAU - Holthuysen, Astrid E M
AU  - Holthuysen AE
FAU - Sloetjes, Annet W
AU  - Sloetjes AW
FAU - Koch, Alisa E
AU  - Koch AE
FAU - Radstake, Timothy R D J
AU  - Radstake TR
FAU - van den Berg, Wim B
AU  - van den Berg WB
LA  - eng
GR  - AR48267/AR/NIAMS NIH HHS/United States
GR  - R01 HL058695/HL/NHLBI NIH HHS/United States
GR  - AI40987/AI/NIAID NIH HHS/United States
GR  - R01 AR048267/AR/NIAMS NIH HHS/United States
GR  - HL58695/HL/NHLBI NIH HHS/United States
GR  - R01 AI040987/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
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.
DEP - 20050126
PL  - England
TA  - Arthritis Res Ther
JT  - Arthritis research & therapy
JID - 101154438
RN  - 0 (Chemokines)
RN  - 0 (Fcgr1 protein, mouse)
RN  - 0 (Interleukin-1)
RN  - 0 (Interleukin-13)
RN  - 0 (Oligopeptides)
RN  - 0 (Peptide Fragments)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, IgG)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (peptide VDIPEN)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - Adenoviridae/genetics
MH  - Animals
MH  - Arthritis, Experimental/immunology/pathology/*prevention & control
MH  - Cartilage, Articular/*pathology
MH  - Cell Death
MH  - Chemokines/biosynthesis/genetics
MH  - Chondrocytes/*pathology
MH  - Extracellular Matrix/*metabolism
MH  - Gene Expression Regulation
MH  - *Genetic Therapy
MH  - Genetic Vectors/genetics/*therapeutic use
MH  - Immune Complex Diseases/pathology/*prevention & control
MH  - Interleukin-1/biosynthesis/genetics
MH  - Interleukin-13/genetics/*physiology
MH  - Knee Joint
MH  - Male
MH  - Matrix Metalloproteinases/genetics/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Oligopeptides/*biosynthesis/genetics
MH  - Peptide Fragments/*biosynthesis/genetics
MH  - RNA, Messenger/biosynthesis
MH  - Receptors, IgG/biosynthesis/genetics
MH  - Recombinant Fusion Proteins/physiology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Synovial Membrane/metabolism
MH  - Transduction, Genetic
PMC - PMC1065337
EDAT- 2005/03/04 09:00
MHDA- 2005/12/16 09:00
PMCR- 2005/01/26
CRDT- 2005/03/04 09:00
PHST- 2004/07/29 00:00 [received]
PHST- 2004/12/09 00:00 [revised]
PHST- 2004/12/22 00:00 [accepted]
PHST- 2005/03/04 09:00 [pubmed]
PHST- 2005/12/16 09:00 [medline]
PHST- 2005/03/04 09:00 [entrez]
PHST- 2005/01/26 00:00 [pmc-release]
AID - ar1502 [pii]
AID - 10.1186/ar1502 [doi]
PST - ppublish
SO  - Arthritis Res Ther. 2005;7(2):R392-401. doi: 10.1186/ar1502. Epub 2005 Jan 26.