| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
B kinases 
and 
in serum- and
IL-1-induced human VSMC proliferation
Division of Nephrology, Department of Medicine and Tupper Research Institute, New England Medical Center Hospitals, Tufts University School of Medicine, Boston, Massachusetts 02111
Interleukin-1 (IL-1) is a potent vascular smooth muscle
cell (VSMC) mitogen, which can stimulate cells via activation of
nuclear factor-
B (NF-B) following phosphorylation of its
inhibitory subunit (IB). Because the proliferative effect of IL-1 is
additive with that of serum, the present studies assessed the role of
IB kinases (IKKs) and NF-B in both IL-1- and serum-induced VSMC proliferation. IL-1
(1 ng/ml) induced marked and persistent NF-B activation in VSMC that was maximal at 1 h and persisted for 3 days.
There was a 3-fold increase in DNA synthesis after acute IL-1 exposure
(24-96 h) and a 12-fold increase after chronic IL-1 exposure (>7
days). Electrophoretic mobility shift assay and supershift analysis
indicated that IL-1-induced NF-B complexes consisted of p65/p50
heterodimers and p50 homodimers. Human saphenous vein smooth muscle
cells (HSVSMC) were transiently cotransfected with expression plasmids
encoding a dominant negative mutant form of either IKK
or IKK, in
which K44 was mutated to A (K44A), and a green fluorescent
protein expression plasmid that allows identification of transfected
cells. IL-1 induced nuclear localization of p65 in 95% of cells
transfected with vector alone but in only 69% and 26% of cells
expressing IKK (K44A) or IKK (K44A), respectively. Likewise,
proliferation increased 3.2-fold in IL-1-treated HSVSMC which had been
transfected with vector alone, but only 2.2- and 1.5-fold proliferation
in HSVSMC expressing IKK (K44A) or IKK (K44A), respectively.
Although serum activated NF-B transiently, serum-induced
proliferation was markedly attenuated in HSVSMC expressing IKK
(K44A) and IKK (K44A) compared with HSVSMC transfected with vector
alone. The results support an essential role of IKKs in the
proliferative response of HSVSMC to IL-1 and to serum.
nuclear factor-B; dominant negative mutant; cell transfection; interleukin-1; vascular smooth muscle cells
This article has been cited by other articles:
|
|
 |
|
  X. Zhu, Y. Lin, M. Bacanamwo, L. Chang, R. Chai, I. Massud, J. Zhang, M. T. Garcia-Barrio, W. E. Thompson, and Y. E. Chen Interleukin-1 {beta}-induced Id2 gene expression is mediated by Egr-1 in vascular smooth muscle cells Cardiovasc Res, October 1, 2007; 76(1): 141 - 148. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Yang, V. Murthy, K. Schultz, J. B. Tatro, K. A. Fitzgerald, and D. Beasley Toll-like receptor 3 signaling evokes a proinflammatory and proliferative phenotype in human vascular smooth muscle cells Am J Physiol Heart Circ Physiol, November 1, 2006; 291(5): H2334 - H2343. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Schultz, B. L. Fanburg, and D. Beasley Hypoxia and hypoxia-inducible factor-1{alpha} promote growth factor-induced proliferation of human vascular smooth muscle cells Am J Physiol Heart Circ Physiol, June 1, 2006; 290(6): H2528 - H2534. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Yang, D. Coriolan, V. Murthy, K. Schultz, D. T. Golenbock, and D. Beasley Proinflammatory phenotype of vascular smooth muscle cells: role of efficient Toll-like receptor 4 signaling Am J Physiol Heart Circ Physiol, September 1, 2005; 289(3): H1069 - H1076. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. V. Sharma, M. V. Gurjar, and R. C. Bhalla Genome and Hormones: Gender Differences in Physiology: Selected Contribution: Estrogen receptor-alpha gene transfer inhibits proliferation and NF-kappa B activation in VSM cells from female rats J Appl Physiol, November 1, 2001; 91(5): 2400 - 2406. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
