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

First Author  Mukai S Year  2018
Journal  FASEB J Volume  32
Issue  8 Pages  4085-4095
PubMed ID  29490166 Mgi Jnum  J:276856
Mgi Id  MGI:6307388 Doi  10.1096/fj.201700176R
Citation  Mukai S, et al. (2018) Inhibition of Vascular Adhesion Protein-1 for Treatment of Graft-Versus-Host Disease in Mice. FASEB J 32(8):4085-4095
abstractText  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.-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.
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