title: Stimulatory interactions between human coronary smooth muscle cells and dendritic cells.
abstract: Despite inflammatory and immune mechanisms participating to atherogenesis and dendritic cells (DCs) driving immune and non-immune tissue injury response, the interactions between DCs and vascular smooth muscle cells (VSMCs) possibly relevant to vascular pathology including atherogenesis are still unclear. To address this issue, immature DCs (iDCs) generated from CD14+ cells isolated from healthy donors were matured either with cytokines (mDCs), or co-cultured (ccDCs) with human coronary artery VSMCs (CASMCs) using transwell chambers. Co-culture induced DC immunophenotypical and functional maturation similar to cytokines, as demonstrated by flow cytometry and mixed lymphocyte reaction. In turn, factors from mDCs and ccDCs induced CASMC migration. MCP-1 and TNFα, secreted from DCs, and IL-6 and MCP-1, secreted from CASMCs, were primarily involved. mDCs adhesion to CASMCs was enhanced by CASMC pre-treatment with IFNγ and TNFα ICAM-1 and VCAM-1 were involved, since the expression of specific mRNAs for these molecules increased and adhesion was inhibited by neutralizing antibodies to the counter-receptors CD11c and CD18. Adhesion was also inhibited by CASMC pre-treatment with the HMG-CoA-reductase inhibitor atorvastatin and the PPARγ agonist rosiglitazone, which suggests a further mechanism for the anti-inflammatory action of these drugs. Adhesion of DCs to VSMCs was shown also in vivo in rat carotid 7 to 21 days after crush and incision injury. The findings indicate that DCs and VSMCs can interact with reciprocal stimulation, possibly leading to perpetuate inflammation and vascular wall remodelling, and that the interaction is enhanced by a cytokine-rich inflammatory environment and down-regulated by HMGCoA-reductase inhibitors and PPARγ agonists.
authors.affiliation: Department of Health Sciences, Clinical Pharmacology and Oncology Unit, University of Florence, Florence, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Paccosi
authors.affiliation: Department of Health Sciences, Clinical Pharmacology and Oncology Unit, University of Florence, Florence, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Musilli
authors.affiliation: Central Laboratory, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Caporale
authors.affiliation: Central Laboratory, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy.
authors.forename: Anna Maria Grazia
authors.initials: AM
authors.lastname: Gelli
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Guasti
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.
authors.forename: Ann Maria
authors.initials: AM
authors.lastname: Clemente
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.
authors.forename: Maria Gabriella
authors.initials: MG
authors.lastname: Torcia
authors.affiliation: Department of Medicine and Surgery, University of Salerno, Salerno, Italy.
authors.forename: Amelia
authors.initials: A
authors.lastname: Filippelli
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Romagnoli
authors.affiliation: Department of Health Sciences, Clinical Pharmacology and Oncology Unit, University of Florence, Florence, Italy.
authors.forename: Astrid
authors.initials: A
authors.lastname: Parenti
mesh_terms: D000818:Animals; D000069059:Atorvastatin; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D060833:Cellular Microenvironment / Q000187:drug effects; D018920:Coculture Techniques; D003331:Coronary Vessels / Q000166:cytology*; D016207:Cytokines / Q000494:pharmacology; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D006538:Heptanoic Acids / Q000494:pharmacology; D006801:Humans; D016130:Immunophenotyping; D007249:Inflammation / Q000473:pathology; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D010641:Phenotype; D011758:Pyrroles / Q000494:pharmacology; D017208:Rats, Wistar; D000077154:Rosiglitazone; D012995:Solubility; D045162:Thiazolidinediones / Q000494:pharmacology
chemical_list: D015815:Cell Adhesion Molecules; D016207:Cytokines; D006538:Heptanoic Acids; D011758:Pyrroles; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D000069059:Atorvastatin