PMID- 16473828
OWN - NLM
STAT- MEDLINE
DCOM- 20060323
LR  - 20171116
IS  - 1074-7613 (Print)
IS  - 1074-7613 (Linking)
VI  - 24
IP  - 2
DP  - 2006 Feb
TI  - Double-stranded RNA-mediated TLR3 activation is enhanced by CD14.
PG  - 153-63
AB  - CD14 is a well-known pattern-recognition receptor in the innate immune system. 
      Here, we show that CD14 enhances double-stranded RNA (dsRNA)-mediated Toll-like 
      receptor 3 (TLR3) activation. Bone marrow-derived macrophages (BMDMs) from 
      CD14-/- mice exhibited impaired responses to polyinosine-polycytidylic acid 
      (pIpC) and reduced production of inflammatory cytokines. CD14-/- mice injected 
      with pIpC also showed impaired cytokine production. When tested with [32P] 
      labeled pIpC small fragments (pIpCsf) that maintain the inflammatory activity of 
      crude pIpC, CD14 directly bound pIpCsf and mediated cellular uptake of pIpCsf. 
      Our data show that TLR3 is intracellular and directly interacts with CD14. 
      Internalized pIpCsf was localized in the lysosomes via the endosomes. In 
      unstimulated cells, neither CD14 nor TLR3 was detected in the lysosomes. However, 
      TLR3 was localized in the lysosomes as was CD14 once the cells took up pIpC. We 
      also observed that internalized pIpCsf colocalized with CD14 and TLR3. 
      Consequently, CD14 mediates pIpC uptake and enhances TLR3 signaling.
FAU - Lee, Hyun-Ku
AU  - Lee HK
AD  - Department of Immunology, The Scripps Research Institute, La Jolla, California 
      92037, USA.
FAU - Dunzendorfer, Stefan
AU  - Dunzendorfer S
FAU - Soldau, Katrin
AU  - Soldau K
FAU - Tobias, Peter S
AU  - Tobias PS
LA  - eng
GR  - AI59753/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Immunity
JT  - Immunity
JID - 9432918
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Lipopolysaccharide Receptors)
RN  - 0 (NF-kappa B)
RN  - 0 (Phosphatidylcholines)
RN  - 0 (RNA, Double-Stranded)
RN  - 0 (Toll-Like Receptor 3)
RN  - 6931-84-6 (1-palmitoyl-2-linoleoylphosphatidylcholine)
SB  - IM
CIN - Immunity. 2006 Feb;24(2):127-9. PMID: 16473824
MH  - Adaptor Proteins, Signal Transducing/metabolism
MH  - Animals
MH  - CHO Cells
MH  - Cells, Cultured
MH  - Cricetinae
MH  - Cricetulus
MH  - Cytoplasmic Vesicles/metabolism
MH  - Humans
MH  - Lipopolysaccharide Receptors/genetics/*physiology
MH  - Macrophages/*immunology
MH  - Mice
MH  - Mice, Knockout
MH  - NF-kappa B/metabolism
MH  - Phosphatidylcholines/pharmacology
MH  - RNA, Double-Stranded/*metabolism
MH  - Toll-Like Receptor 3/*metabolism
MH  - Transfection
EDAT- 2006/02/14 09:00
MHDA- 2006/03/24 09:00
CRDT- 2006/02/14 09:00
PHST- 2005/06/15 00:00 [received]
PHST- 2005/11/17 00:00 [revised]
PHST- 2005/12/27 00:00 [accepted]
PHST- 2006/02/14 09:00 [pubmed]
PHST- 2006/03/24 09:00 [medline]
PHST- 2006/02/14 09:00 [entrez]
AID - S1074-7613(06)00003-3 [pii]
AID - 10.1016/j.immuni.2005.12.012 [doi]
PST - ppublish
SO  - Immunity. 2006 Feb;24(2):153-63. doi: 10.1016/j.immuni.2005.12.012.