PMID- 16782847
OWN - NLM
STAT- MEDLINE
DCOM- 20070112
LR  - 20200930
IS  - 0363-6135 (Print)
IS  - 0363-6135 (Linking)
VI  - 291
IP  - 5
DP  - 2006 Nov
TI  - Toll-like receptor 3 signaling evokes a proinflammatory and proliferative 
      phenotype in human vascular smooth muscle cells.
PG  - H2334-43
AB  - Inflammation plays a key role in atherogenesis, perhaps promoted by bacterial and 
      viral products present within the artery wall. Vascular smooth muscle cells 
      (VSMC) can express certain bacterially responsive Toll-like receptors (TLR), 
      which promote a proinflammatory and proliferative VSMC phenotype when activated, 
      but it is unknown whether virally activated TLR can regulate VSMC phenotype. Here 
      we tested the role in VSMC of TLR3, which is activated by double-stranded 
      (dsRNA), a molecular signature of viruses. VSMC from multiple vessel types, 
      including human coronary artery (HCoASMC) and mouse aorta (MAoSMC), expressed 
      TLR3 constitutively, and HCoASMC were exquisitely sensitive to dsRNA-stimulated 
      release of monocyte chemoattractant protein-1 (MCP-1) and interleukin-6. 
      dsRNA-induced MCP-1 release was abolished by small interfering RNA-mediated TLR3 
      knockdown in HCoASMC and was absent in TLR3-/- MAoSMC but was unimpaired in 
      TLR2-/- and in TLR4 signaling-deficient MAoSMC. Exposure to dsRNA also activated 
      ERK1/2 and NF-kappaB in both human and murine SMC, but these effects were absent 
      in SMC from TLR3-deficient mice, demonstrating a crucial role of TLR3 signaling. 
      dsRNA also stimulated proliferation of HCoASMC, indicated by increased DNA 
      synthesis, and induced persistent elevations in the intracellular levels of 
      growth-promoting mediators, including interleukin-1alpha and phospho-ERK1/2. We 
      conclude that exposure of HCoASMC to dsRNA elicits dramatic TLR3-mediated 
      proinflammatory and proproliferative phenotypic changes, responses that could 
      potentially be triggered by viral infection of cells within the arterial wall.
FAU - Yang, Xin
AU  - Yang X
AD  - Tufts-New England Medical Center, Box 8486, 750 Washington St., Boston, MA 02111, 
      USA.
FAU - Murthy, Vanishree
AU  - Murthy V
FAU - Schultz, Kelly
AU  - Schultz K
FAU - Tatro, Jeffrey B
AU  - Tatro JB
FAU - Fitzgerald, Katherine A
AU  - Fitzgerald KA
FAU - Beasley, Debbie
AU  - Beasley D
LA  - eng
GR  - HL-47569/HL/NHLBI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20060616
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (Toll-Like Receptor 3)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Cell Culture Techniques
MH  - Cell Division/*physiology
MH  - Cells, Cultured
MH  - Child, Preschool
MH  - Coronary Vessels/cytology
MH  - Female
MH  - Humans
MH  - Male
MH  - Muscle, Smooth, Vascular/cytology/*physiology
MH  - Phenotype
MH  - Pulmonary Artery/cytology
MH  - Signal Transduction/*immunology
MH  - Toll-Like Receptor 3/genetics/*metabolism
MH  - Vasculitis/immunology/*physiopathology
EDAT- 2006/06/20 09:00
MHDA- 2007/01/16 09:00
CRDT- 2006/06/20 09:00
PHST- 2006/06/20 09:00 [pubmed]
PHST- 2007/01/16 09:00 [medline]
PHST- 2006/06/20 09:00 [entrez]
AID - 00252.2006 [pii]
AID - 10.1152/ajpheart.00252.2006 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2006 Nov;291(5):H2334-43. doi: 
      10.1152/ajpheart.00252.2006. Epub 2006 Jun 16.