PMID- 17056568
OWN - NLM
STAT- MEDLINE
DCOM- 20061213
LR  - 20190516
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 177
IP  - 9
DP  - 2006 Nov 1
TI  - Engagement of CD14 mediates the inflammatory potential of monosodium urate 
      crystals.
PG  - 6370-8
AB  - Phagocyte ingestion of monosodium urate (MSU) crystals can induce proinflammatory 
      responses and trigger acute gouty inflammation. Alternatively, the uptake of MSU 
      crystals by mature macrophages can be noninflammatory and promote resolution of 
      gouty inflammation. Macrophage activation by extracellular MSU crystals involves 
      apparent recognition and ingestion mediated by TLR2 and TLR4, with subsequent 
      intracellular recognition linked to caspase-1 activation and IL-1beta processing 
      driven by the NACHT-LRR-PYD-containing protein-3 inflammasome. In this study, we 
      examined the potential role in gouty inflammation of CD14, a phagocyte-expressed 
      pattern recognition receptor that functionally interacts with both TLR2 and TLR4. 
      MSU crystals, but not latex beads, directly bound recombinant soluble (s) CD14 in 
      vitro. CD14(-/-) bone marrow-derived macrophages (BMDMs) demonstrated unimpaired 
      phagocytosis of MSU crystals but reduced p38 phosphorylation and approximately 
      90% less IL-1beta and CXCL1 release. Attenuated MSU crystal-induced IL-1beta 
      release in CD14(-/-) BMDMs was mediated by decreased pro-IL-1beta protein 
      expression and additionally by decreased caspase-1 activation and IL-1beta 
      processing consistent with diminished NACHT-LRR-PYD-containing protein-3 
      inflammasome activation. Coating of MSU crystals with sCD14, but not sTLR2 or 
      sTLR4, restored IL-1beta and CXCL1 production in CD14(-/-) BMDMs in vitro. Gain 
      of function of CD14 directly enhanced TLR4-mediated signaling in response to MSU 
      crystals in transfected Chinese hamster ovary cells in vitro. Last, MSU 
      crystal-induced leukocyte influx at 6 h was reduced by approximately 75%, and 
      local induction of IL-1beta decreased by >80% in CD14(-/-) mouse s.c. air pouches 
      in vivo. We conclude that engagement of CD14 is a central determinant of the 
      inflammatory potential of MSU crystals.
FAU - Scott, Peter
AU  - Scott P
AD  - Veterans Affairs Medical Center, Department of Medicine, University of 
      California-San Diego, San Diego, CA 92161, USA.
FAU - Ma, Hong
AU  - Ma H
FAU - Viriyakosol, Suganya
AU  - Viriyakosol S
FAU - Terkeltaub, Robert
AU  - Terkeltaub R
FAU - Liu-Bryan, Ru
AU  - Liu-Bryan R
LA  - eng
GR  - AR 049416/AR/NIAMS NIH HHS/United States
GR  - HL 077360/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Chemokines, CXC)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Lipopolysaccharide Receptors)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Toll-Like Receptor 4)
RN  - 268B43MJ25 (Uric Acid)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 3.4.22.36 (Caspase 1)
SB  - IM
MH  - Animals
MH  - CHO Cells
MH  - Caspase 1/metabolism
MH  - Chemokines, CXC/metabolism
MH  - Cricetinae
MH  - Crystallization
MH  - Enzyme Activation
MH  - Gout/*immunology/metabolism
MH  - Inflammation/immunology/metabolism
MH  - Interleukin-1beta/metabolism
MH  - Lipopolysaccharide Receptors/genetics/*metabolism
MH  - Macrophages/drug effects/*immunology
MH  - Mice
MH  - *Phagocytosis/genetics
MH  - Recombinant Proteins/chemistry/genetics/metabolism
MH  - Toll-Like Receptor 4/metabolism
MH  - Uric Acid/chemistry/*metabolism/pharmacology
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
EDAT- 2006/10/24 09:00
MHDA- 2006/12/14 09:00
CRDT- 2006/10/24 09:00
PHST- 2006/10/24 09:00 [pubmed]
PHST- 2006/12/14 09:00 [medline]
PHST- 2006/10/24 09:00 [entrez]
AID - 177/9/6370 [pii]
AID - 10.4049/jimmunol.177.9.6370 [doi]
PST - ppublish
SO  - J Immunol. 2006 Nov 1;177(9):6370-8. doi: 10.4049/jimmunol.177.9.6370.