The Prolyl Hydroxylase Inhibitor Dimethyl Oxalyl Glycine Decreases Early Gastrointestinal GVHD in Experimental Allogeneic Hematopoietic Cell Transplantation

Senthilnathan Palaniyandi, Reena Kumari, Sabarinath Venniyil Radhakrishnan, Ethan Strattan, Natalya Hakim, Reinhold Munker, Melissa V. Kesler, Gerhard C. Hildebrandt

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Background. Prolyl hydroxylase inhibitors (PHI) promote stabilization of hypoxia-inducible factor-1 alpha and affect signaling cascades of inflammation and cell death. Their beneficial use in experimental models of ulcerative colitis and lung allograft rejection led us to test the effect of the PHI dimethyl oxalyl glycine (DMOG) in the pathophysiology of graft versus host disease (GVHD). Methods. Acute GVHD was induced in lethally irradiated BALB/c mice. DMOG was administered intraperitoneally on alternate days for the first 2-weeks posttransplant, and then twice a week till day +50, while controls received vehicle only. Animals were monitored for clinical GVHD and analyzed at day +7 and at day +50. Results. DMOG treatment of allogeneic recipients improved survival by day +50, which was associated with decreased early gut injury and serum tumor necrosis factor-α compared with allogeneic controls. DMOG treatment of allogeneic recipients resulted in increased hypoxia-inducible factor-1 alpha expression and reduced apoptosis in the terminal ileum via Fas-associated protein with death domain protein repression along with decreased T-cell infiltration. Reduced pathology in colon after DMOG treatment associates with intestinal epithelium integrity and reduced damage caused by diminished recruitment of neutrophils. Conclusions. Taken together, we show protective effects of DMOG on early gut GVHD and improved survival in a model of allogeneic hematopoietic cell transplantation, providing the rationale for further evaluation of PHIs, in the prevention and treatment of acute GVHD.

Original languageEnglish
Pages (from-to)2507-2515
Number of pages9
JournalTransplantation
Volume104
Issue number12
DOIs
StatePublished - Dec 1 2020

Bibliographical note

Publisher Copyright:
© 2020 Lippincott Williams and Wilkins. All rights reserved.

ASJC Scopus subject areas

  • Transplantation

Fingerprint

Dive into the research topics of 'The Prolyl Hydroxylase Inhibitor Dimethyl Oxalyl Glycine Decreases Early Gastrointestinal GVHD in Experimental Allogeneic Hematopoietic Cell Transplantation'. Together they form a unique fingerprint.

Cite this