PMID- 19269957
OWN - NLM
STAT- MEDLINE
DCOM- 20090618
LR  - 20171116
IS  - 1462-0332 (Electronic)
IS  - 1462-0324 (Linking)
VI  - 48
IP  - 5
DP  - 2009 May
TI  - A novel paradigm for dendritic cells as effectors of cartilage destruction.
PG  - 502-7
LID - 10.1093/rheumatology/kep040 [doi]
AB  - OBJECTIVE: Dendritic cells (DCs) are enriched in RA synovium and have been 
      implicated in the pathogenesis of RA primarily through their ability to present 
      autoantigen and activate T cells. However, whether DCs play an effector role in 
      cartilage destruction is unknown. The aim of this study was to investigate 
      whether DCs can induce collagen release from cartilage and the mechanism 
      involved. METHODS: Human monocyte-derived DCs (mDCs) were activated with CD40 
      ligand (CD40L) to mimic DC-T-cell interaction, and supernatants were incubated 
      with cartilage explants. Hydroxyproline was assessed as a measure of collagen 
      release and collagenolytic activity was measured by a bioassay using tritiated 
      collagen. TNF-alpha in DC supernatants was measured by specific ELISA. RESULTS: 
      Supernatants from CD40L-activated mDCs, but not unstimulated mDCs, strongly 
      induced the destruction of cartilage collagen. mDC supernatants did not contain 
      collagenases but did induce collagenolytic activity in cartilage explants. 
      Neutralization of TNF-alpha in mDC supernatants completely abolished 
      collagenolysis. CONCLUSIONS: This study shows that mDCs, upon CD40-ligation, 
      induce cartilage collagen degradation through an indirect mechanism via the 
      production of TNF-alpha. Our data suggest a potential important role for 
      mDC-derived TNF-alpha in RA, which is in line with the previously reported 
      observations that DCs are a major source of TNF-alpha in early autoimmune lesions 
      and that anti-TNF-alpha therapeutics effectively suppress joint damage in RA 
      patients. We propose that DCs can act as effectors in cartilage destruction, 
      adding a new aspect to the functional role of DCs in RA pathogenesis.
FAU - Lakey, Rachel L
AU  - Lakey RL
AD  - Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle 
      University, Newcastle upon Tyne, UK.
FAU - Morgan, Tanya G
AU  - Morgan TG
FAU - Rowan, Andrew D
AU  - Rowan AD
FAU - Isaacs, John D
AU  - Isaacs JD
FAU - Cawston, Tim E
AU  - Cawston TE
FAU - Hilkens, Catharien M U
AU  - Hilkens CM
LA  - eng
GR  - Arthritis Research UK/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090305
PL  - England
TA  - Rheumatology (Oxford)
JT  - Rheumatology (Oxford, England)
JID - 100883501
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Immunoglobulin gamma-Chains)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 147205-72-9 (CD40 Ligand)
RN  - 39QXN67537 (Ro 45-2081)
RN  - 9007-34-5 (Collagen)
RN  - B72HH48FLU (Infliximab)
RN  - EC 3.4.24.- (Collagenases)
SB  - IM
MH  - Antibodies, Monoclonal/pharmacology
MH  - Arthritis, Rheumatoid/*immunology
MH  - CD40 Ligand/metabolism
MH  - Cartilage, Articular/drug effects/*immunology
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Collagen/metabolism
MH  - Collagenases/metabolism
MH  - Dendritic Cells/*immunology
MH  - Humans
MH  - Immunoglobulin gamma-Chains/pharmacology
MH  - Infliximab
MH  - Receptors, Tumor Necrosis Factor
MH  - Recombinant Fusion Proteins/pharmacology
MH  - Tumor Necrosis Factor-alpha/antagonists & inhibitors/biosynthesis/physiology
MH  - Up-Regulation
EDAT- 2009/03/10 09:00
MHDA- 2009/06/19 09:00
CRDT- 2009/03/10 09:00
PHST- 2009/03/10 09:00 [entrez]
PHST- 2009/03/10 09:00 [pubmed]
PHST- 2009/06/19 09:00 [medline]
AID - kep040 [pii]
AID - 10.1093/rheumatology/kep040 [doi]
PST - ppublish
SO  - Rheumatology (Oxford). 2009 May;48(5):502-7. doi: 10.1093/rheumatology/kep040. 
      Epub 2009 Mar 5.