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 1

Fingerprint

Graft vs Host Disease
Grafts
Blood Vessels
Adhesion
Proteins
Therapeutics
Inflammation
Transplants
Transplantation (surgical)
Hematopoietic Stem Cell Transplantation
Stem cells
Fibrosis
Tissue

Keywords

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

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Inhibition of Vascular Adhesion Protein-1 for Treatment of Graft-Versus-Host Disease in Mice. / Mukai, Shin; Ogawa, Yoko; Kawakami, Yutaka; Mashima, Yukihiko; Tsubota, Kazuo.

In: FASEB Journal, Vol. 32, No. 8, 01.08.2018, p. 4085-4095.

Research output: Contribution to journalArticle

Mukai, Shin ; Ogawa, Yoko ; Kawakami, Yutaka ; Mashima, Yukihiko ; Tsubota, Kazuo. / Inhibition of Vascular Adhesion Protein-1 for Treatment of Graft-Versus-Host Disease in Mice. In: FASEB Journal. 2018 ; Vol. 32, No. 8. pp. 4085-4095.
@article{38cb6457822b4c6f88e307d7de9adc86,
title = "Inhibition of Vascular Adhesion Protein-1 for Treatment of Graft-Versus-Host Disease in Mice",
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.",
keywords = "Age-associated disease, Fibrosis, Inflammation, Inhibitor, Refractory disease",
author = "Shin Mukai and Yoko Ogawa and Yutaka Kawakami and Yukihiko Mashima and Kazuo Tsubota",
year = "2018",
month = "8",
day = "1",
doi = "10.1096/fj.201700176R",
language = "English",
volume = "32",
pages = "4085--4095",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "8",

}

TY - JOUR

T1 - Inhibition of Vascular Adhesion Protein-1 for Treatment of Graft-Versus-Host Disease in Mice

AU - Mukai, Shin

AU - Ogawa, Yoko

AU - Kawakami, Yutaka

AU - Mashima, Yukihiko

AU - Tsubota, Kazuo

PY - 2018/8/1

Y1 - 2018/8/1

N2 - 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.

AB - 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.

KW - Age-associated disease

KW - Fibrosis

KW - Inflammation

KW - Inhibitor

KW - Refractory disease

UR - http://www.scopus.com/inward/record.url?scp=85050862665&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85050862665&partnerID=8YFLogxK

U2 - 10.1096/fj.201700176R

DO - 10.1096/fj.201700176R

M3 - Article

VL - 32

SP - 4085

EP - 4095

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 8

ER -