Cigarette smoke extract promotes human vascular smooth muscle cell proliferation and survival through ERK1/2- and NF-κB-dependent pathways.
(2010) In The Scientific World Journal 10. p.2139-2156- Abstract
- Tobacco use is one of the major risk factors of cardiovascular disease. The underlying molecular mechanisms that link cigarette smoke to cardiovascular disease remain unclear. The present study was designed to examine the effects of dimethyl sulfoxide (DMSO)-soluble smoke particles (DSPs) on human aortic smooth muscle cell (HASMC) cultures, and to explore the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) and nuclear factor-kappaB (NF-κB) signal mechanisms involved. Serum-starved HASMCs were treated with DSPs for up to 48 h. DSPs promoted cell proliferation in a concentration-dependent manner from 0.05 to 0.2 μl/ml. Activation of ERK1/2 and NF-κB was seen after exposure to DSPs. This... (More)
- Tobacco use is one of the major risk factors of cardiovascular disease. The underlying molecular mechanisms that link cigarette smoke to cardiovascular disease remain unclear. The present study was designed to examine the effects of dimethyl sulfoxide (DMSO)-soluble smoke particles (DSPs) on human aortic smooth muscle cell (HASMC) cultures, and to explore the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) and nuclear factor-kappaB (NF-κB) signal mechanisms involved. Serum-starved HASMCs were treated with DSPs for up to 48 h. DSPs promoted cell proliferation in a concentration-dependent manner from 0.05 to 0.2 μl/ml. Activation of ERK1/2 and NF-κB was seen after exposure to DSPs. This occurred in parallel with the increase in cell population, bromodeoxyuridine incorporation, and cyclinD1/cyclin-dependent kinase 4 expression. Blocking phosphorylation of ERK1/2 by MAPK inhibitors U0126 and PD98059, and inhibiting activation of NF-κB by IkappaB (IκB) kinase inhibitors wedelolactone or IMD-0354, abolished the DSP effects. However, either a p38 inhibitor (SB203580) or an inhibitor of lipopolysaccharide (polymyxin B), or nicotinic receptor blockers (mecamylamine and alpha-bungarotoxin), did not inhibit a DSP-induced increase in the cell population. DSPs increased the expression of intercellular adhesion molecule 1 and the release of interleukin-6 in HASMCs, both of which were inhibited by ERK1/2 or NF-κB pathway inhibitors. Furthermore, cell apoptosis and necrosis were found in serum-starved HASMCs. DSPs decreased cell death and increased B-cell leukemia/lymphoma 2 expression. Blocking phosphorylation of ERK1/2 or NF-κB attenuated DSP-induced cell death inhibition. Cigarette smoke particles stimulate HASMC proliferation and inhibit cell death. The intracellular signal mechanisms behind this involve activation of ERK1/2 and NF-κB pathways. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1732216
- author
- Chen, Qingwen LU ; Edvinsson, Lars LU and Xu, Cang-Bao LU
- organization
- publishing date
- 2010
- type
- Contribution to journal
- publication status
- published
- subject
- in
- The Scientific World Journal
- volume
- 10
- pages
- 2139 - 2156
- publisher
- Hindawi Limited
- external identifiers
-
- wos:000283936000005
- pmid:21057728
- scopus:78650260882
- pmid:21057728
- ISSN
- 2356-6140
- DOI
- 10.1100/tsw.2010.201
- language
- English
- LU publication?
- yes
- id
- 837326a5-40ee-4972-b3f5-b07846bef524 (old id 1732216)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/21057728?dopt=Abstract
- date added to LUP
- 2016-04-04 09:43:22
- date last changed
- 2024-10-13 05:35:58
@article{837326a5-40ee-4972-b3f5-b07846bef524,
abstract = {{Tobacco use is one of the major risk factors of cardiovascular disease. The underlying molecular mechanisms that link cigarette smoke to cardiovascular disease remain unclear. The present study was designed to examine the effects of dimethyl sulfoxide (DMSO)-soluble smoke particles (DSPs) on human aortic smooth muscle cell (HASMC) cultures, and to explore the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) and nuclear factor-kappaB (NF-κB) signal mechanisms involved. Serum-starved HASMCs were treated with DSPs for up to 48 h. DSPs promoted cell proliferation in a concentration-dependent manner from 0.05 to 0.2 μl/ml. Activation of ERK1/2 and NF-κB was seen after exposure to DSPs. This occurred in parallel with the increase in cell population, bromodeoxyuridine incorporation, and cyclinD1/cyclin-dependent kinase 4 expression. Blocking phosphorylation of ERK1/2 by MAPK inhibitors U0126 and PD98059, and inhibiting activation of NF-κB by IkappaB (IκB) kinase inhibitors wedelolactone or IMD-0354, abolished the DSP effects. However, either a p38 inhibitor (SB203580) or an inhibitor of lipopolysaccharide (polymyxin B), or nicotinic receptor blockers (mecamylamine and alpha-bungarotoxin), did not inhibit a DSP-induced increase in the cell population. DSPs increased the expression of intercellular adhesion molecule 1 and the release of interleukin-6 in HASMCs, both of which were inhibited by ERK1/2 or NF-κB pathway inhibitors. Furthermore, cell apoptosis and necrosis were found in serum-starved HASMCs. DSPs decreased cell death and increased B-cell leukemia/lymphoma 2 expression. Blocking phosphorylation of ERK1/2 or NF-κB attenuated DSP-induced cell death inhibition. Cigarette smoke particles stimulate HASMC proliferation and inhibit cell death. The intracellular signal mechanisms behind this involve activation of ERK1/2 and NF-κB pathways.}},
author = {{Chen, Qingwen and Edvinsson, Lars and Xu, Cang-Bao}},
issn = {{2356-6140}},
language = {{eng}},
pages = {{2139--2156}},
publisher = {{Hindawi Limited}},
series = {{The Scientific World Journal}},
title = {{Cigarette smoke extract promotes human vascular smooth muscle cell proliferation and survival through ERK1/2- and NF-κB-dependent pathways.}},
url = {{http://dx.doi.org/10.1100/tsw.2010.201}},
doi = {{10.1100/tsw.2010.201}},
volume = {{10}},
year = {{2010}},
}