NDLI: Halofugine prevents cutaneous graft versus host disease by suppression of Th17 differentiation.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Cheng, Hai Tian, Jing Zeng, Lingyu Pan, Bin Li, Zhenyu Song, Guoliang Chen, Wei Xu, Kailin
Description	Country affiliation: China Author Affiliation: Cheng H ( The Affiliated Hospital of Xuzhou Medical College, Xuzhou, China.)
Abstract	Halofuginone, isolated from Dichroa febreifuga, is a potent inhibitor of skin collagen in chronic graft-versus-host disease (GVHD). To evaluate the effect of halofuginone on the development of cutaneous GVHD, we developed a murine model based on BALB/c (H-2d) as recipients with transplantation of C57BL/6(H-2b) bone marrow plus splenocytes. Halofuginone or its vehicle dimethyl sulfoxide (DMSO) was given introperitoneally at a dose of 5 ug/mouse daily from one day before transplantation until 20 days post-transplantation. Halofuginone-treated recipients showed only very mild appearance of cutaneous GVHD, whereas DMSO-treated recipients rapidly showed manifestation of severe cutaneous GVHD, indicating a protective effect of halofuginone in cutaneous GVHD. After injected with halofuginone, we observed a decrease in the number of CD4(+) interleukin (IL)-17(+) cells and a parallel increase in that of CD4(+) interferon (IFN)-gamma(+) cells in peripheral blood. This shift between CD4(+) IL-17(+) cells and CD4(+) IFN-gamma(+) cells developed through modulation of cytokine profile indicated by a marked increase in the levels of IFN-gamma, tumor necrosis factor (TNF)-alpha, and IL-6. The level of IL-10 was not changed obviously. Mechanistically, we demonstrate that severe tissue damage was associated with the production of IL-17 and expansion of CD4(+)IL-17(+) cells during this disorder. Specific inhibition of Th17 differentiation by halofuginone reduced disease severity. Our results indicate a significant role of halofuginone in suppressing cutaneous GVHD, apparently through effect on inhibition of Th17 cells differentiation.
File Format	HTM / HTML
ISSN	10245332
Issue Number	5
Volume Number	17
e-ISSN	16078454
Journal	Hematology
Language	English
Publisher	Taylor & Francis
Publisher Date	2012-09-01
Publisher Place	Great Britain (UK)
Access Restriction	Subscribed
Subject Keyword	Discipline Hematology Angiogenesis Inhibitors Pharmacology Bone Marrow Transplantation Cell Differentiation Drug Effects Graft Vs Host Disease Prevention & Control Piperidines Quinazolinones Skin Diseases Th17 Cells Immunology Animals Chronic Disease Cytokines Female Pathology Male Mice Mice, Inbred Balb C Time Factors Transplantation, Homologous Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Hematology

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