Interleukin 10 attenuates neointimal proliferation and inflammation in aortic allografts by a heme oxygenase-dependent pathway.
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.
Chen
Sifeng
S
Department of Medicine, Nephrology Research and Training Center, University of Alabama at Birmingham, Birmingham, AL 35294.
Kapturczak
Matthias H
MH
Wasserfall
Clive
C
Glushakova
Olena Y
OY
Campbell-Thompson
Martha
M
Deshane
Jessy S
JS
Joseph
Reny
R
Cruz
Pedro E
PE
Hauswirth
William W
WW
Madsen
Kirsten M
KM
Croker
Byron P
BP
Berns
Kenneth I
KI
Atkinson
Mark A
MA
Flotte
Terence R
TR
Tisher
C Craig
CC
Agarwal
Anupam
A
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
D006360:Heat-Shock Proteins; D016753:Interleukin-10; D010105:Oxygenases; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat