title: IL10 released by a new inflammation-regulated lentiviral system efficiently attenuates zymosan-induced arthritis.
abstract: Administration of anti-inflammatory cytokines is a common therapeutic strategy in chronic inflammatory diseases. Gene therapy is an efficient method for delivering therapeutic molecules to target cells. Expression of the cell adhesion molecule E-selectin (ESEL), which is expressed in the early stages of inflammation, is controlled by proinflammatory cytokines, making its promoter a good candidate for the design of inflammation-regulated gene therapy vectors. This study describes an ESEL promoter (ESELp)-based lentiviral vector (LV) that drives localized transgene expression during inflammation. Mouse matrigel plug assays with ESELp-transduced endothelial cells showed that systemic lipopolysaccharide (LPS) administration selectively induces ESELp-controlled luciferase expression in vivo. Inflammation-specific induction was confirmed in a mouse model of arthritis, showing that this LV is repeatedly induced early in acute inflammation episodes and is downregulated during remission. Moreover, the local acute inflammatory response in this animal model was efficiently blocked by expression of the anti-inflammatory cytokine interleukin-10 (IL10) driven by our LV system. This inflammation-regulated expression system has potential application in the design of new strategies for the local treatment of chronic inflammatory diseases such as cardiovascular and autoimmune diseases.
authors: Department of Molecular Biology, Universidad Autónoma de Madrid, Madrid, Spain.
authors: Guillermo
authors: G
authors: Garaulet
authors: Arántzazu
authors: A
authors: Alfranca
authors: María
authors: M
authors: Torrente
authors: Amelia
authors: A
authors: Escolano
authors: Raquel
authors: R
authors: López-Fontal
authors: Sonsoles
authors: S
authors: Hortelano
authors: Juan M
authors: JM
authors: Redondo
authors: Antonio
authors: A
authors: Rodríguez
mesh_terms: D000818:Animals; D001168:Arthritis / Q000139:chemically induced / Q000517:prevention & control*; D003094:Collagen; D004338:Drug Combinations; D005822:Genetic Vectors; D007249:Inflammation / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism*; D007797:Laminin; D016086:Lentivirus / Q000235:genetics*; D051379:Mice; D011509:Proteoglycans; D019076:Transgenes; D015054:Zymosan / Q000009:adverse effects*
chemical_list: D004338:Drug Combinations; D018836:Inflammation Mediators; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D016753:Interleukin-10; D003094:Collagen; D015054:Zymosan