Inhibition of Vascular Adhesion Protein-1 for Treatment of Graft-Versus-Host Disease in Mice

Shin Mukai, Yoko Ogawa, Yutaka Kawakami, Yukihiko Mashima, Kazuo Tsubota

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Graft-versus-host disease (GVHD) is a potentially lethal complication of hematopoietic stem cell transplantation (HSCT). GVHD comprises acute and chronic forms. To date, several approaches to treat acute GVHD or chronic GVHD have been reported. However, there is no literature precedent regarding all-in-one methods to address the 2 GVHD types. Severe inflammation in organs affected by GVHD is highly problematic, and vascular adhesion protein-1 (VAP-1) is known to be detrimentally involved in various inflammatory diseases. Based on the previous reports, we envisaged that there would be a link between GVHD and VAP-1, and we strived to create effective therapies for the 2 types of GVHD using a mouse model of GVHD. Our investigation indicated that expression of VAP-1 was elevated in organs disordered by GVHD. Hence, we subsequently attempted to block VAP-1 by using a novel inhibitor. Our results indicate that systemic injection of the inhibitor prevented aberrant influx of inflammatory cells into tissues and thereby mitigate GVHD-elicited inflammation and fibrosis. Collectively, our study suggests that the increased expression of VAP-1 is detrimentally associated with the development of GVHD and that the blockade of VAP-1 could be a promising medical modality to combat the acute and chronic variants.

Original languageEnglish
Pages (from-to)4085-4095
Number of pages11
JournalFASEB Journal
Volume32
Issue number8
DOIs
Publication statusPublished - 2018 Aug

Keywords

  • Age-associated disease
  • Fibrosis
  • Inflammation
  • Inhibitor
  • Refractory disease

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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