PMID- 18369152
OWN - NLM
STAT- MEDLINE
DCOM- 20080701
LR  - 20240316
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 111
IP  - 11
DP  - 2008 Jun 1
TI  - Regulation of tumor necrosis factor receptor-1 and the IKK-NF-kappaB pathway by 
      LDL receptor-related protein explains the antiinflammatory activity of this 
      receptor.
PG  - 5316-25
LID - 10.1182/blood-2007-12-127613 [doi]
AB  - Low-density lipoprotein receptor-related protein (LRP-1) functions in endocytosis 
      and in cell signaling directly (by binding signaling adaptor proteins) or 
      indirectly (by regulating levels of other cell-surface receptors). Because recent 
      studies in rodents suggest that LRP-1 inhibits inflammation, we conducted 
      activity-based protein profiling experiments to discover novel proteases, 
      involved in inflammation, that are regulated by LRP-1. We found that activated 
      complement proteases accumulate at increased levels when LRP-1 is absent. 
      Although LRP-1 functions as an endocytic receptor for C1r and C1s, complement 
      protease mRNA expression was increased in LRP-1-deficient cells, as was 
      expression of inducible nitric oxide synthase (iNOS) and interleukin-6. 
      Regulation of expression of inflammatory mediators was explained by the ability 
      of LRP-1 to suppress basal cell signaling through the I kappaB kinase-nuclear 
      factor-kappaB (NF-kappaB) pathway. LRP-1-deficient macrophages, isolated from 
      mice, demonstrated increased expression of iNOS, C1r, and monocyte 
      chemoattractant protein-1 (MCP-1); MCP-1 expression was inhibited by NF-kappaB 
      antagonism. The mechanism by which LRP-1 inhibits NF-kappaB activity involves 
      down-regulating cell-surface tumor necrosis factor receptor-1 (TNFR1) and thus, 
      inhibition of autocrine TNFR1-initiated cell signaling. TNF-alpha-neutralizing 
      antibody inhibited NF-kappaB activity selectively in LRP-1-deficient cells. We 
      propose that LRP-1 suppresses expression of inflammatory mediators indirectly, by 
      regulating TNFR1-dependent cell signaling through the I kappaB kinase-NF-kappaB 
      pathway.
FAU - Gaultier, Alban
AU  - Gaultier A
AD  - Department of Pathology, University of California San Diego School of Medicine, 
      La Jolla, CA 92093-0612, USA.
FAU - Arandjelovic, Sanja
AU  - Arandjelovic S
FAU - Niessen, Sherry
AU  - Niessen S
FAU - Overton, Cheryl D
AU  - Overton CD
FAU - Linton, MacRae F
AU  - Linton MF
FAU - Fazio, Sergio
AU  - Fazio S
FAU - Campana, W Marie
AU  - Campana WM
FAU - Cravatt, Benjamin F 3rd
AU  - Cravatt BF 3rd
FAU - Gonias, Steven L
AU  - Gonias SL
LA  - eng
GR  - R01 HL-60551/HL/NHLBI NIH HHS/United States
GR  - R01 HL086988/HL/NHLBI NIH HHS/United States
GR  - R01 HL065405/HL/NHLBI NIH HHS/United States
GR  - R01 HL086988-02/HL/NHLBI NIH HHS/United States
GR  - R01 HL065405-08/HL/NHLBI NIH HHS/United States
GR  - R01 CA087660/CA/NCI NIH HHS/United States
GR  - R01 HL060551/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20080327
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (LDL-Receptor Related Protein-Associated Protein)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 9007-36-7 (Complement System Proteins)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Cells, Cultured
MH  - Complement Activation/*physiology
MH  - Complement System Proteins
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Electrophoretic Mobility Shift Assay
MH  - Flow Cytometry
MH  - Gene Expression
MH  - Gene Expression Regulation
MH  - I-kappa B Kinase/*metabolism
MH  - Inflammation/metabolism
MH  - LDL-Receptor Related Protein-Associated Protein/*metabolism
MH  - Mice
MH  - NF-kappa B/*metabolism
MH  - Polymerase Chain Reaction
MH  - RNA, Messenger/analysis
MH  - Receptors, Tumor Necrosis Factor, Type I/*metabolism
MH  - Signal Transduction/physiology
PMC - PMC2396725
EDAT- 2008/03/29 09:00
MHDA- 2008/07/02 09:00
PMCR- 2009/06/01
CRDT- 2008/03/29 09:00
PHST- 2008/03/29 09:00 [pubmed]
PHST- 2008/07/02 09:00 [medline]
PHST- 2008/03/29 09:00 [entrez]
PHST- 2009/06/01 00:00 [pmc-release]
AID - S0006-4971(20)47137-X [pii]
AID - 2007/127613 [pii]
AID - 10.1182/blood-2007-12-127613 [doi]
PST - ppublish
SO  - Blood. 2008 Jun 1;111(11):5316-25. doi: 10.1182/blood-2007-12-127613. Epub 2008 
      Mar 27.