title: Interleukin 10 attenuates neointimal proliferation and inflammation in aortic allografts by a heme oxygenase-dependent pathway.
abstract: Interleukin 10 (IL-10) is a pleiotropic cytokine with well known antiinflammatory, immunosuppressive, and immunostimulatory properties. Chronic allograft rejection, characterized by vascular neointimal proliferation, is a major cause of organ transplant loss, particularly in heart and kidney transplant recipients. In a Dark Agouti to Lewis rat model of aortic transplantation, we evaluated the effects of a single intramuscular injection of a recombinant adeno-associated viral vector (serotype 1) encoding IL-10 (rAAV1-IL-10) on neointimal proliferation and inflammation. rAAV1-IL-10 treatment resulted in a significant reduction of neointimal proliferation and graft infiltration with macrophages and T and B lymphocytes. The mechanism underlying the protective effects of IL-10 in aortic allografts involved heme oxygenase 1 (HO-1) because inhibition of HO activity reversed not only neointimal proliferation but also inflammatory cell infiltration. Our results indicate that IL-10 attenuates neointimal proliferation and inflammatory infiltration and strongly imply that HO-1 is an important intermediary through which IL-10 regulates the inflammatory responses associated with chronic vascular rejection.
authors.affiliation: Department of Medicine, Nephrology Research and Training Center, University of Alabama at Birmingham, Birmingham, AL 35294.
authors.forename: Sifeng
authors.initials: S
authors.lastname: Chen
authors.forename: Matthias H
authors.initials: MH
authors.lastname: Kapturczak
authors.forename: Clive
authors.initials: C
authors.lastname: Wasserfall
authors.forename: Olena Y
authors.initials: OY
authors.lastname: Glushakova
authors.forename: Martha
authors.initials: M
authors.lastname: Campbell-Thompson
authors.forename: Jessy S
authors.initials: JS
authors.lastname: Deshane
authors.forename: Reny
authors.initials: R
authors.lastname: Joseph
authors.forename: Pedro E
authors.initials: PE
authors.lastname: Cruz
authors.forename: William W
authors.initials: WW
authors.lastname: Hauswirth
authors.forename: Kirsten M
authors.initials: KM
authors.lastname: Madsen
authors.forename: Byron P
authors.initials: BP
authors.lastname: Croker
authors.forename: Kenneth I
authors.initials: KI
authors.lastname: Berns
authors.forename: Mark A
authors.initials: MA
authors.lastname: Atkinson
authors.forename: Terence R
authors.initials: TR
authors.lastname: Flotte
authors.forename: C Craig
authors.initials: CC
authors.lastname: Tisher
authors.forename: Anupam
authors.initials: A
authors.lastname: Agarwal
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001011:Aorta / Q000637:transplantation*; D015153:Blotting, Western; D049109:Cell Proliferation; D000229:Dependovirus; D042783:Endothelial Cells / Q000166:cytology; D004797:Enzyme-Linked Immunosorbent Assay; D005822:Genetic Vectors; D006084:Graft Rejection / Q000378:metabolism / Q000517:prevention & control*; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing); D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control*; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D010105:Oxygenases / Q000378:metabolism*; D051381:Rats; D019076:Transgenes / Q000235:genetics; D014184:Transplantation, Homologous
chemical_list: D006360:Heat-Shock Proteins; D016753:Interleukin-10; D010105:Oxygenases; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat