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Inhibition of Vascular Adhesion Protein‐1 for Treatment of Graft‐Versus‐Host Disease in Mice
Author(s) -
Mukai Shin,
Ogawa Yoko,
Kawakami Yutaka,
Mashima Yukihiko,
Tsubota Kazuo
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201700176r
Subject(s) - graft versus host disease , medicine , inflammation , hematopoietic stem cell transplantation , immunology , disease , haematopoiesis , fibrosis , transplantation , stem cell , pathology , biology , genetics
Graft‐versus‐host disease (GVHD) is a potentially lethal complication of hematopoietic stem cell trans‐plantation (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.—Mukai, S., Ogawa, Y., Kawakami, Y., Mashima, Y., Tsubota, K. Inhibition of vascular adhesion protein‐1 for treatment of graft‐versus‐host disease in mice. FASEB J . 32, 4085–4095 (2018). www.fasebj.org