AJP - Heart Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Am J Physiol Heart Circ Physiol (January 28, 2005). doi:10.1152/ajpheart.00919.2004
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
288/6/H2946    most recent
00919.2004v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Zampetaki, A.
Right arrow Articles by Xu, Q.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zampetaki, A.
Right arrow Articles by Xu, Q.
Submitted on September 2, 2004
Accepted on January 24, 2005

Biomechanical Stress Induces IL-6 Expression in Smooth Muscle Cells via Ras/Rac1-p38 MAPK-NF-{kappa}B Signalling Pathways

Anna Zampetaki1*, Zhongyi Zhang1, Yanhua Hu1, and Qingbo Xu1

1 Cardiac and Vascular Sciences, St. George's Hospital Medical School, London, United Kingdom

* To whom correspondence should be addressed. E-mail: azampeta{at}sghms.ac.uk.

IL-6, a pro-inflammatory cytokine has been implicated in the development of vascular diseases. We previously demonstrated that mechanical stress can initiate signalling pathways leading to smooth muscle cell (SMC) proliferation and apoptosis, but little is known concerning strain stress-induced inflammatory response. To explore the role of stretch in the upregulation of cytokine expression in SMCs we performed RNase protection assay for a panel of cytokines, and found that mechanical stress resulted in a time dependent induction of IL-6 mRNA, but not other cytokines, e.g. IL-1{alpha}, IL-1{beta}, IL-6, IL-10, IL-12p35, IL-12p40, IL-18, IFN{gamma} and MIF. This induction also correlated with elevated IL-6 protein levels in the supernatant. Pretreatment of the cells with NF-{kappa}B inhibitors inhibited NF-{kappa}B activity and resulted in a marked inhibition (50%) of IL-6 protein. Moreover, SMC lines stably expressing dominant negative Ras (RasN17) or Rac (RacN17) exhibited a remarkable decrease in p38MAPK activity and IL-6 mRNA induction by mechanical stress. Furthermore, a significant inhibition of 30% and 40% in IL-6 protein was observed in SMCs pretreated with inhibitors of p38MAPK and ERK1/2, but not JNK. Interestingly, SMCs isolated from PKCdelta-deficient mice exhibited higher levels of IL-6 compared to wild-type cells. Finally, high levels of IL-6 expression were observed in atherosclerotic lesions of apoE-deficient mice and vein bypass grafts, which are related to altered biomechanical stress. Our findings demonstrate that biomechanical stress-induced IL-6 expression occurs via a mechanism that involves Ras/Rac-p38MAPK-NF-{kappa}B-NF-IL6 signalling pathways, which is downregulated by PKCdelta, and suggest that modulation of this event contributes to the pathogenesis of atherosclerosis.




This article has been cited by other articles:


Home page
 Circ. Res.Home page
M. Mayr, A. Zampetaki, A. Sidibe, U. Mayr, X. Yin, A. I. De Souza, Y.-L. Chung, B. Madhu, P. H. Quax, Y. Hu, et al.
Proteomic and Metabolomic Analysis of Smooth Muscle Cells Derived From the Arterial Media and Adventitial Progenitors of Apolipoprotein E-Deficient Mice
Circ. Res., May 9, 2008; 102(9): 1046 - 1056.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
A. Zampetaki, L. Zeng, Q. Xiao, A. Margariti, Y. Hu, and Q. Xu
Lacking cytokine production in ES cells and ES-cell-derived vascular cells stimulated by TNF-{alpha} is rescued by HDAC inhibitor trichostatin A
Am J Physiol Cell Physiol, October 1, 2007; 293(4): C1226 - C1238.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
W. F. Liu, C. M. Nelson, J. L. Tan, and C. S. Chen
Cadherins, RhoA, and Rac1 Are Differentially Required for Stretch-Mediated Proliferation in Endothelial Versus Smooth Muscle Cells
Circ. Res., August 31, 2007; 101(5): e44 - e52.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
S. Riou, B. Mees, B. Esposito, R. Merval, J. Vilar, D. Stengel, E. Ninio, R. van Haperen, R. de Crom, A. Tedgui, et al.
High Pressure Promotes Monocyte Adhesion to the Vascular Wall
Circ. Res., April 27, 2007; 100(8): 1226 - 1233.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
R. Bianchi, C. Adami, I. Giambanco, and R. Donato
S100B binding to RAGE in microglia stimulates COX-2 expression
J. Leukoc. Biol., January 1, 2007; 81(1): 108 - 118.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
V. de Waard, E. K. Arkenbout, M. Vos, A. I.M. Mocking, H. W.M. Niessen, W. Stooker, B. A.J.M. de Mol, P. H.A. Quax, E. N.T.P. Bakker, E. VanBavel, et al.
TR3 Nuclear Orphan Receptor Prevents Cyclic Stretch-Induced Proliferation of Venous Smooth Muscle Cells
Am. J. Pathol., June 1, 2006; 168(6): 2027 - 2035.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
J. Kanefsky, M. Lenburg, and C.-M. Hai
Cholinergic Receptor and Cyclic Stretch-Mediated Inflammatory Gene Expression in Intact ASM
Am. J. Respir. Cell Mol. Biol., April 1, 2006; 34(4): 417 - 425.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 1977 by the American Physiological Society.