title: Interleukin-3 stimulates migration and proliferation of vascular smooth muscle cells: a potential role in atherogenesis.
abstract: 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).
  
  
  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 alpha-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.
authors.affiliation: Department of Internal Medicine, University of Turin, Italy.
authors.forename: M F
authors.initials: MF
authors.lastname: Brizzi
authors.forename: L
authors.initials: L
authors.lastname: Formato
authors.forename: P
authors.initials: P
authors.lastname: Dentelli
authors.forename: A
authors.initials: A
authors.lastname: Rosso
authors.forename: M
authors.initials: M
authors.lastname: Pavan
authors.forename: G
authors.initials: G
authors.lastname: Garbarino
authors.forename: M
authors.initials: M
authors.lastname: Pegoraro
authors.forename: G
authors.initials: G
authors.lastname: Camussi
authors.forename: L
authors.initials: L
authors.lastname: Pegoraro
mesh_terms: D001161:Arteriosclerosis / Q000473:pathology; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D016228:Endothelial Growth Factors / Q000235:genetics; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D015870:Gene Expression; D006801:Humans; D015151:Immunoblotting; D007377:Interleukin-3 / Q000235:genetics / Q000494:pharmacology*; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism; D008222:Lymphokines / Q000235:genetics; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016185:Receptors, Interleukin-3 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007377:Interleukin-3; D008222:Lymphokines; D012333:RNA, Messenger; D016185:Receptors, Interleukin-3; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D004247:DNA; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one