PMID- 24943093
OWN - NLM
STAT- MEDLINE
DCOM- 20141126
LR  - 20191210
IS  - 2326-5205 (Electronic)
IS  - 2326-5191 (Linking)
VI  - 66
IP  - 10
DP  - 2014 Oct
TI  - Macrophage-derived delta-like protein 1 enhances interleukin-6 and matrix 
      metalloproteinase 3 production by fibroblast-like synoviocytes in mice with 
      collagen-induced arthritis.
PG  - 2751-61
LID - 10.1002/art.38743 [doi]
AB  - OBJECTIVE: We previously reported that blockade of the Notch ligand delta-like 
      protein 1 (DLL-1) suppressed osteoclastogenesis and ameliorated arthritis in a 
      mouse model of rheumatoid arthritis (RA). However, the mechanisms by which joint 
      inflammation were suppressed have not yet been revealed. This study was 
      undertaken to determine whether DLL-1 regulates the production of RA-related 
      proinflammatory cytokines. METHODS: Joint cells from mice with collagen-induced 
      arthritis (CIA) and mouse fibroblast-like synoviocytes (FLS) were cultured with 
      or without stimuli in the presence of neutralizing antibodies against Notch 
      ligands, and the production of proinflammatory cytokines was determined by 
      enzyme-linked immunosorbent assay. The expression of Notch receptors and ligands 
      on mouse joint cells was determined by flow cytometry. RESULTS: The production of 
      interleukin-6 (IL-6) and granulocyte-macrophage colony-stimulating factor 
      (GM-CSF) by mouse joint cells with or without stimulation was suppressed by DLL-1 
      blockade. DLL-1 blockade also suppressed the levels of IL-6 and matrix 
      metalloproteinase 3 (MMP-3) in the joint fluid in a mouse model of RA. However, 
      the production of tumor necrosis factor alpha and IL-1beta was not suppressed by DLL-1 
      blockade. The production of IL-6 and MMP-3 by mouse FLS was enhanced by DLL-1 
      stimulation as well as Notch-2 activation. Among joint cells, DLL-1 was not 
      expressed on mouse FLS but was expressed on macrophages. CONCLUSION: These 
      results suggest that the interaction of DLL-1 on mouse joint macrophages with 
      Notch-2 on mouse FLS enhances the production of IL-6 and MMP-3. Therefore, 
      suppression of IL-6, GM-CSF, and MMP-3 production by DLL-1 blockade might be 
      responsible for the amelioration of arthritis in a mouse model of RA.
CI  - Copyright (c) 2014 by the American College of Rheumatology.
FAU - Sekine, Chiyoko
AU  - Sekine C
AD  - Juntendo University School of Medicine, Tokyo, Japan, and Teikyo University 
      School of Medicine, Tokyo, Japan.
FAU - Nanki, Toshihiro
AU  - Nanki T
FAU - Yagita, Hideo
AU  - Yagita H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arthritis Rheumatol
JT  - Arthritis & rheumatology (Hoboken, N.J.)
JID - 101623795
RN  - 0 (Calcium-Binding Proteins)
RN  - 0 (Dlk1 protein, mouse)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Interleukin-6)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Animals
MH  - Arthritis, Experimental/*metabolism
MH  - Arthritis, Rheumatoid/*metabolism
MH  - Calcium-Binding Proteins
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/metabolism
MH  - Intercellular Signaling Peptides and Proteins/*metabolism
MH  - Interleukin-6/*metabolism
MH  - Joints/metabolism
MH  - Male
MH  - Matrix Metalloproteinase 3/*metabolism
MH  - Mice
MH  - Mice, Inbred DBA
MH  - Synovial Fluid/metabolism
MH  - Synovial Membrane/*metabolism
EDAT- 2014/06/20 06:00
MHDA- 2014/12/15 06:00
CRDT- 2014/06/20 06:00
PHST- 2013/09/16 00:00 [received]
PHST- 2014/06/05 00:00 [accepted]
PHST- 2014/06/20 06:00 [entrez]
PHST- 2014/06/20 06:00 [pubmed]
PHST- 2014/12/15 06:00 [medline]
AID - 10.1002/art.38743 [doi]
PST - ppublish
SO  - Arthritis Rheumatol. 2014 Oct;66(10):2751-61. doi: 10.1002/art.38743.