PMID- 18311795
OWN - NLM
STAT- MEDLINE
DCOM- 20080428
LR  - 20211020
IS  - 0004-3591 (Print)
IS  - 0004-3591 (Linking)
VI  - 58
IP  - 3
DP  - 2008 Mar
TI  - Mediation of the proinflammatory cytokine response in rheumatoid arthritis and 
      spondylarthritis by interactions between fibroblast-like synoviocytes and natural 
      killer cells.
PG  - 707-17
LID - 10.1002/art.23264 [doi]
AB  - OBJECTIVE: Fibroblast-like synoviocytes (FLS) are potentially directly involved 
      in the propagation of inflammation. We have previously shown evidence of an 
      expanded activated population of natural killer (NK) cells in spondylarthritis 
      (SpA) patients. In the present study, we sought to determine whether the 
      interaction between NK cells and FLS from SpA patients results in a 
      proinflammatory response. METHODS: Autologous NK cells and FLS were obtained from 
      6 patients with SpA, 4 patients with rheumatoid arthritis (RA), and 8 patients 
      with osteoarthritis (OA). Physical interactions between NK cells and FLS were 
      studied by time-lapse phase-contrast microscopy. Fluorescence-activated cell 
      sorting was used to study the activation, proliferation, and survival of NK cells 
      in contact with FLS. Cytokine and stromal factor production were measured by a 
      multiple cytokine bead assay. RESULTS: NK cells both adhered to and migrated 
      beneath the FLS monolayer (pseudoemperipolesis). FLS from SpA and RA patients 
      supported increased pseudoemperipolesis, activation, cytokine production, and 
      survival of NK cells. The production of proinflammatory cytokines, including 
      interleukin-6 (IL-6), IL-8, IL-1beta, and IL-15, was increased in cocultures of 
      NK cells and FLS, particularly in those from RA and SpA patients. Production of 
      interferon-gamma, RANTES, and matrix metalloproteinase 3 (MMP-3) by NK cell and 
      FLS coculture was greatest in SpA patients. Surface expression of IL-15 on FLS 
      was significantly increased in SpA and RA patients, but not OA patients. Blockade 
      with an IL-15 monoclonal antibody resulted in increased apoptosis of NK cells. 
      CONCLUSION: FLS promote the migration, activation, and survival of NK cells. The 
      interaction of NK cells with FLS results in increased IL-15 expression by FLS and 
      the production of proinflammatory chemokines, cytokines, and MMPs, which may 
      contribute to joint inflammation. This response was much more marked in SpA and 
      RA patients as compared with OA patients.
FAU - Chan, Antoni
AU  - Chan A
AD  - Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular 
      Medicine, John Radcliffe Hospital, Oxford, UK. achan@hammer.imm.ox.ac.uk
FAU - Filer, Andrew
AU  - Filer A
FAU - Parsonage, Greg
AU  - Parsonage G
FAU - Kollnberger, Simon
AU  - Kollnberger S
FAU - Gundle, Roger
AU  - Gundle R
FAU - Buckley, Christopher D
AU  - Buckley CD
FAU - Bowness, Paul
AU  - Bowness P
LA  - eng
GR  - G116/131/MRC_/Medical Research Council/United Kingdom
GR  - MC_U137884185/MRC_/Medical Research Council/United Kingdom
GR  - ARC_/Arthritis Research UK/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arthritis Rheum
JT  - Arthritis and rheumatism
JID - 0370605
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CCL5)
RN  - 0 (Cytokines)
RN  - 0 (Interleukin-15)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Interleukin-6)
RN  - 0 (Interleukin-8)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Arthritis, Rheumatoid/*metabolism/pathology
MH  - Cell Communication/physiology
MH  - Cells, Cultured
MH  - Chemokine CCL2/metabolism
MH  - Chemokine CCL5/metabolism
MH  - Cytokines/*metabolism
MH  - Female
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/metabolism
MH  - Humans
MH  - Interferon-gamma/metabolism
MH  - Interleukin-15/metabolism
MH  - Interleukin-1beta/metabolism
MH  - Interleukin-6/metabolism
MH  - Interleukin-8/metabolism
MH  - Killer Cells, Natural/*metabolism/*pathology
MH  - Male
MH  - Matrix Metalloproteinase 3/metabolism
MH  - Middle Aged
MH  - Osteoarthritis, Knee/metabolism/pathology
MH  - Spondylarthritis/*metabolism/pathology
MH  - Synovial Membrane/*metabolism/*pathology
EDAT- 2008/03/04 09:00
MHDA- 2008/04/29 09:00
CRDT- 2008/03/04 09:00
PHST- 2008/03/04 09:00 [pubmed]
PHST- 2008/04/29 09:00 [medline]
PHST- 2008/03/04 09:00 [entrez]
AID - 10.1002/art.23264 [doi]
PST - ppublish
SO  - Arthritis Rheum. 2008 Mar;58(3):707-17. doi: 10.1002/art.23264.