(Circulation. 2001;103:549.)
© 2001 American Heart Association, Inc.
Basic Science Reports |
Interleukin-3 Stimulates Migration and Proliferation of Vascular Smooth Muscle Cells
A Potential Role in Atherogenesis
From the Department of Internal Medicine, University of Turin (M.F.B., L.F., P.D., A.R., M.P., G.G., G.C., L.P.), and the Division of Vascular Surgery, Ospedale Molinette (M.P.), Turin, Italy.
Correspondence to Luigi Pegoraro, Department of Internal Medicine, University of Turin, Corso Dogliotti 14, 10126 Turin, Italy.
Background—Cytokines released by activated T lymphocytes are key regulators of chronic inflammatory response, including atherosclerosis. The aim of this study was to investigate the presence of interleukin-3 (IL-3) in lymphocytes infiltrating the atherosclerotic plaque and the effect of this cytokine on primary vascular smooth muscle cells (SMCs).
Methods and
Results—Twenty atherosclerotic carotid
arterial specimens and 5 early atherosclerotic lesions from the
internal carotid were manually minced to fragments, and T lymphocytes
infiltrating the atherosclerotic plaque were isolated on solid-phase
anti-CD3 polystyrene plates. Southern blot analysis demonstrated that
in all samples, lymphocytes expressed IL-3 and IL-2 receptor 
-chain
transcripts, indicating that in this context, the activated T
lymphocytes may release IL-3. We further analyzed the expression of the
IL-3 receptor and the biological effects exerted by the ligand on
vascular SMCs. ß-IL-3–transducing subunit was detected both on
cultured SMCs and on endothelial cells and SMCs within atheroma. The
analysis of the IL-3–induced biological effects demonstrated that it
was able to trigger both mitogenic and motogenic signals. Moreover, we
demonstrated that the addition of PD98059, a known inhibitor of the
MAP–extracellular signaling-regulated/MAP kinase pathway, completely
inhibited IL-3–mediated MAP kinase activation and IL-3–induced
migration and proliferation. Finally, IL-3 was found to stimulate
vascular endothelial growth factor (VEGF) gene
transcription.
Conclusions—IL-3, expressed by activated T lymphocytes infiltrating early and advanced atherosclerotic plaques, may sustain the atherosclerotic process either directly, by activating SMC migration and proliferation, or indirectly, via VEGF production.
Key Words: atherosclerosis • smooth muscle cells • cytokines • signal transduction
This article has been cited by other articles:
 |
|
 |
|
  J. Chen, J. Olsen, S. Ford, S. Mirza, A. Walker, J. M. Murphy, and I. G. Young A New Isoform of Interleukin-3 Receptor {alpha} with Novel Differentiation Activity and High Affinity Binding Mode J. Biol. Chem., February 27, 2009; 284(9): 5763 - 5773. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Zeoli, P. Dentelli, A. Rosso, G. Togliatto, A. Trombetta, L. Damiano, P. F. di Celle, L. Pegoraro, F. Altruda, and M. F. Brizzi Interleukin-3 promotes expansion of hemopoietic-derived CD45+ angiogenic cells and their arterial commitment via STAT5 activation Blood, July 15, 2008; 112(2): 350 - 361. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Oren, A. R. Erbay, M. Balci, and S. Cehreli Role of Novel Biomarkers of Inflammation in Patients With Stable Coronary Heart Disease Angiology, April 1, 2007; 58(2): 148 - 155. [Abstract] [PDF]
|
|
|
|
 |
|
 A. Tedgui and Z. Mallat Cytokines in Atherosclerosis: Pathogenic and Regulatory Pathways Physiol Rev, April 1, 2006; 86(2): 515 - 581. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. H. Walter, J. Haendeler, J. Reinhold, U. Rochwalsky, F. Seeger, J. Honold, J. Hoffmann, C. Urbich, R. Lehmann, F. Arenzana-Seisdesdos, et al. Impaired CXCR4 Signaling Contributes to the Reduced Neovascularization Capacity of Endothelial Progenitor Cells From Patients With Coronary Artery Disease Circ. Res., November 25, 2005; 97(11): 1142 - 1151. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. W. Raines and N. Ferri Thematic Review Series: The Immune System and Atherogenesis. Cytokines affecting endothelial and smooth muscle cells in vascular disease J. Lipid Res., June 1, 2005; 46(6): 1081 - 1092. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Defilippi, A. Rosso, P. Dentelli, C. Calvi, G. Garbarino, G. Tarone, L. Pegoraro, and M. F. Brizzi {beta}1 integrin and IL-3R coordinately regulate STAT5 activation and anchorage-dependent proliferation J. Cell Biol., March 28, 2005; 168(7): 1099 - 1108. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Calvi, P. Dentelli, M. Pagano, A. Rosso, M. Pegoraro, S. Giunti, G. Garbarino, G. Camussi, L. Pegoraro, and M. F. Brizzi Angiopoietin 2 Induces Cell Cycle Arrest in Endothelial Cells: A Possible Mechanism Involved in Advanced Plaque Neovascularization Arterioscler Thromb Vasc Biol, March 1, 2004; 24(3): 511 - 518. [Abstract] [Full Text]
|
|
|
|
 |
|
 A. Ruiz-Torres, R. Lozano, J. Melon, and R. Carraro Age-Dependent Decline of In Vitro Migration (Basal and Stimulated by IGF-1 or Insulin) of Human Vascular Smooth Muscle Cells J. Gerontol. A Biol. Sci. Med. Sci., December 1, 2003; 58(12): B1074 - 1077. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Modi, A. Patel, R. Terrell, R. M. Tuttle, and G. L. Francis Papillary Thyroid Carcinomas from Young Adults and Children Contain a Mixture of Lymphocytes J. Clin. Endocrinol. Metab., September 1, 2003; 88(9): 4418 - 4425. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Von der Thusen, J. Kuiper, T. J. C. Van Berkel, and E. A. L. Biessen Interleukins in Atherosclerosis: Molecular Pathways and Therapeutic Potential Pharmacol. Rev., March 1, 2003; 55(1): 133 - 166. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Jacob, J. D. Molkentin, A. Smolenski, S. M. Lohmann, and N. Begum Insulin inhibits PDGF-directed VSMC migration via NO/ cGMP increase of MKP-1 and its inactivation of MAPKs Am J Physiol Cell Physiol, September 1, 2002; 283(3): C704 - C713. [Abstract] [Full Text] [PDF]
|
|