The synthetic triterpenoid, CDDO, suppresses alloreactive T cell responses and reduces murine early acute graft-versus-host disease mortality.

The synthetic triterpenoid, CDDO, suppresses alloreactive T cell responses and reduces murine early acute graft-versus-host disease mortality. Research Abstract Details 

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The synthetic triterpenoid, CDDO, suppresses alloreactive T cell responses and reduces murine early acute graft-versus-host disease mortality. Abstract Text:

Kai Sun,Minghui Li,Marina Konopleva,Sergej Konoplev,L Clifton Stephens,Steven M Kornblau,Olga Frolova,Danice E C Wilkins,Weihong Ma,Lisbeth A Welniak,Michael Andreeff,William J Murphy,

Acute graft-versus-host disease (aGVHD) still remains one of the life-threatening complications following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Immunomodulation of alloreactive donor T cell responses, as well as cytokine secretion is a potential therapeutic approach for the prevention of aGVHD. The synthetic triterpenoid, CDDO (2-cyano-3, 12-dioxooleana-1, 9-dien-28-oic acid), exhibits potent antitumor activity and has also been shown to mediate anti-inflammatory and immunomodulatory effects. We therefore wanted to assess the effects of CDDO on early lethal aGVHD. In this study, we found that CDDO significantly inhibited in vitro mixed lymphocyte responses and preferentially promoted the apoptosis of proliferating but not resting alloreactive T cells. Using a full major histocompatibility complex (MHC)-disparate murine aGVHD model, we found that the administration of CDDO immediately after transplantation significantly decreased liver pathology as determined by histologic assessment and prolonged survival in mice. Importantly, administration of CDDO did not adversely impair donor myeloid reconstitution as determined by peripheral blood cell count and the extent of donor chimerism. These findings indicate that CDDO has a significant immunomodulatory effects in vitro and on early lethal aGVHD development, particularly affecting the liver, in a murine allo-HSCT model.

The synthetic triterpenoid, CDDO, suppresses alloreactive T cell responses and reduces murine early acute graft-versus-host disease mortality. Publishing Authors By Initials

K Sun,M Li,M Konopleva,S Konoplev,LC Stephens,SM Kornblau,O Frolova,DE Wilkins,W Ma,LA Welniak,M Andreeff,WJ Murphy,

For similar surgical procedures, operative: transplantation: transplantation, homologous research abstracts see: surgical procedures, operative: transplantation: transplantation, homologous research

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The synthetic triterpenoid, CDDO, suppresses alloreactive T cell responses and reduces murine early acute graft-versus-host disease mortality. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Biology of blood and marrow transplantation : jour

VOLUME: 13

Page Numbers: 521-9

Journal Abbreviation:

ISSN: 1083-8791

DAY: 26

MONTH: 02

YEAR: 2007

The synthetic triterpenoid, CDDO, suppresses alloreactive T cell responses and reduces murine early acute graft-versus-host disease mortality. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9600628

The synthetic triterpenoid, CDDO, suppresses alloreactive T cell responses and reduces murine early acute graft-versus-host disease mortality. Keywords Mesh Terms:

KEYWORDS: Transplantation, Homologous

MESH TERMS: adverse effects

Chemical & Substance for Abstract: The synthetic triterpenoid, CDDO, suppresses alloreactive T cell responses and reduces murine early acute graft-versus-host disease mortality. Information

Substance Name: Oleanolic Acid

Registry Number: 508-02-1

Grant and Affiliation Information for The synthetic triterpenoid, CDDO, suppresses alloreactive T cell responses and reduces murine early acute graft-versus-host disease mortality.

AFFILIATION: Department of Microbiology and Immunology, University of Nevada, Reno, Nevada, USA.

Country: United States

AGENCY: United States NCI

GRANT: R01 CA102282

ACRONYM: CA

MEDLINETA: Biol Blood Marrow Transplant

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