PMID- 17293495
OWN - NLM
STAT- MEDLINE
DCOM- 20070802
LR  - 20220317
IS  - 0363-6135 (Print)
IS  - 0363-6135 (Linking)
VI  - 292
IP  - 6
DP  - 2007 Jun
TI  - Endogenous interleukin-1 alpha promotes a proliferative and proinflammatory 
      phenotype in human vascular smooth muscle cells.
PG  - H2927-34
AB  - During vascular disease and following injury, vascular smooth muscle cells (VSMC) 
      proliferate and produce inflammation-promoting cytokines and chemokines. Similar 
      phenotypic changes can be elicited in vitro by activation of Toll-like receptors 
      (TLR) within VSMC. TLR-activated VSMC also produce IL-1 alpha, but it is unknown 
      whether endogenous IL-1 alpha stimulates VSMC in an autocrine manner. Here we 
      tested the hypothesis that endogenous IL-1 alpha contributes to TLR-induced 
      proliferation and chemokine release in human VSMC by using RNA interference to 
      knock down IL-1 alpha expression. Knockdown of IL-1 alpha abolished TLR-induced 
      proliferation and suppressed TLR4-induced release of monocyte chemoattractant 
      protein-1 (MCP-1) by VSMC, indicating that endogenous IL-1 alpha plays a crucial 
      role in both responses. Serum, PDGF, FGF-2, and EGF each increased cellular IL-1 
      alpha concentrations, and IL-1 alpha knockdown inhibited serum- and PDGF-induced 
      DNA synthesis, further indicating that endogenous IL-1 alpha also contributed to 
      VSMC responses to growth factors. IL-1 receptor antagonist, a competitive 
      inhibitor of IL-1 receptor I (IL-1RI), also attenuated TLR-induced proliferation 
      and both basal and TLR-induced MCP-1 expression, indicating at least a partial 
      role of the IL-1RI in mediating these responses. The results support the 
      hypothesis that autocrine actions of endogenous IL-1 alpha, mediated at least in 
      part via IL-1RI signaling, contribute to a proproliferative and proinflammatory 
      phenotypic shift in TLR-activated human VSMC, which might play a pathogenic role 
      in vascular disorders.
FAU - Schultz, Kelly
AU  - Schultz K
AD  - Molecular Cardiology Research Institute, Tufts-New England Medical Center, Box 
      8486, 750 Washington St., Boston, MA 02111, USA.
FAU - Murthy, Vanishree
AU  - Murthy V
FAU - Tatro, Jeffrey B
AU  - Tatro JB
FAU - Beasley, Debbie
AU  - Beasley D
LA  - eng
GR  - HL47569/HL/NHLBI NIH HHS/United States
GR  - HL64853/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20070209
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin 1 Receptor Antagonist Protein)
RN  - 0 (Interleukin-1alpha)
RN  - 0 (Platelet-Derived Growth Factor)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, Interleukin-1 Type I)
RN  - 0 (TLR3 protein, human)
RN  - 0 (TLR4 protein, human)
RN  - 0 (Toll-Like Receptor 3)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Toll-Like Receptors)
RN  - 103107-01-3 (Fibroblast Growth Factor 2)
RN  - 62229-50-9 (Epidermal Growth Factor)
SB  - IM
MH  - *Autocrine Communication
MH  - *Cell Proliferation
MH  - Cells, Cultured
MH  - Chemokine CCL2/metabolism
MH  - Coronary Vessels/metabolism/pathology/physiopathology
MH  - Epidermal Growth Factor/metabolism
MH  - Fibroblast Growth Factor 2/metabolism
MH  - Humans
MH  - Inflammation/*metabolism/pathology/physiopathology
MH  - Interleukin 1 Receptor Antagonist Protein/metabolism
MH  - Interleukin-1alpha/genetics/*metabolism
MH  - Muscle, Smooth, Vascular/*metabolism/pathology/physiopathology
MH  - Myocytes, Smooth Muscle/*metabolism/pathology
MH  - Phenotype
MH  - Platelet-Derived Growth Factor/metabolism
MH  - RNA Interference
MH  - RNA, Small Interfering/genetics/metabolism
MH  - Receptors, Interleukin-1 Type I/*metabolism
MH  - Serum/metabolism
MH  - Toll-Like Receptor 3/metabolism
MH  - Toll-Like Receptor 4/metabolism
MH  - Toll-Like Receptors/*metabolism
MH  - Transfection
EDAT- 2007/02/13 09:00
MHDA- 2007/08/03 09:00
CRDT- 2007/02/13 09:00
PHST- 2007/02/13 09:00 [pubmed]
PHST- 2007/08/03 09:00 [medline]
PHST- 2007/02/13 09:00 [entrez]
AID - 00700.2006 [pii]
AID - 10.1152/ajpheart.00700.2006 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2007 Jun;292(6):H2927-34. doi: 
      10.1152/ajpheart.00700.2006. Epub 2007 Feb 9.