[IL-10 attenuates neointimal proliferation and inflammation in aortic allografts by a heme oxygenase-dependent pathway]
>>Published online before print May 6, 2005
Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0502407102
OPEN ACCESS ARTICLE
Immunology
Interleukin 10 attenuates neointimal proliferation and inflammation in aortic allografts by a heme oxygenase-dependent pathway
( aortic transplantation | chronic transplant rejection | recombinant adeno-associated virus | transplant arteriosclerosis | vascular injury )
Sifeng Chen *, Matthias H. Kapturczak *, Clive Wasserfall , Olena Y. Glushakova , Martha Campbell-Thompson , Jessy S. Deshane *, Reny Joseph *, Pedro E. Cruz ¶||, William W. Hauswirth ¶**, Kirsten M. Madsen , Byron P. Croker , Kenneth I. Berns ¶**, Mark A. Atkinson , Terence R. Flotte ¶||, C. Craig Tisher , and Anupam Agarwal *
*Department of Medicine, Nephrology Research and Training Center, University of Alabama at Birmingham, Birmingham, AL 35294; Departments of Pathology, Medicine, **Molecular Genetics and Microbiology, and ||Pediatrics and ¶University of Florida Genetics Institute and Powell Gene Therapy Center, University of Florida, Gainesville, FL 32610; and Pathology and Laboratory Medicine Service, North Florida/South Georgia Veterans Health Systems, Gainesville, FL 32611
Contributed by Kenneth I. Berns, March 31, 2005
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.<<
pnas.org
Could go on the inflammation thread, but neoinitmal proliferation is definitely a vascular issue.
Cheers, Tuck |
