title: Rosiglitazone prevents graft-versus-host disease (GVHD).
abstract: The effect of rosiglitazone, an agonist of peroxisome proliferator-activated receptor-γ (PPARγ), was investigated in a mouse parent-to-F1 GVHD model. Rosiglitazone inhibited mixed lymphocyte reactions, inducing enhanced apoptosis in CD4+, CD8+, and B220+ cells, but not in NK1.1+, Mac-1+, CD4+/CD25+ and CD3+/NK1.1+ cells. Rosiglitazone administration prevented GVHD in the liver, skin, spleen and intestine. Rosiglitazone inhibited GVHD-induced increases in serum levels of tumor necrosis factor-alpha, interferon-gamma, interleukin (IL)-6, and IL-12, and the GVHD-induced decreases in transforming growth factor-beta and IL-10. Immunophenotyping of splenic leukocytes demonstrated that while rosiglitazone treatment increased the population percentages of both donor and host CD4+/CD25+ and CD3+/NK1.1+ cells, the treatment resulted in lower fractions of both donor and host CD8+ cells. Rosiglitazone inhibited the GVHD-induced decreases in the expression of phosphatase and tensin homologue deleted on chromosome 10 (PTEN), as well as the GVHD-induced increase in the splenic p-Akt and nuclear factor-kappa B expression. These results indicate that rosiglitazone and PPARγ activation may be useful in protecting the host from GVHD.
authors.affiliation: Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Jeonbuk 561-180, Republic of Korea.
authors.forename: Eun-Kee
authors.initials: EK
authors.lastname: Song
authors.forename: Jun-Mo
authors.initials: JM
authors.lastname: Yim
authors.forename: Joo-Yun
authors.initials: JY
authors.lastname: Yim
authors.forename: Min-Young
authors.initials: MY
authors.lastname: Song
authors.forename: Hye-Won
authors.initials: HW
authors.lastname: Rho
authors.forename: Sung Kyun
authors.initials: SK
authors.lastname: Yim
authors.forename: So Yeon
authors.initials: SY
authors.lastname: Jeon
authors.forename: Hee Sun
authors.initials: HS
authors.lastname: Kim
authors.forename: Ho-Young
authors.initials: HY
authors.lastname: Yhim
authors.forename: Na-Ri
authors.initials: NR
authors.lastname: Lee
authors.forename: Jae-Yong
authors.initials: JY
authors.lastname: Kwak
authors.forename: Myung-Hee
authors.initials: MH
authors.lastname: Sohn
authors.forename: Ho Sung
authors.initials: HS
authors.lastname: Park
authors.forename: Kyu Yun
authors.initials: KY
authors.lastname: Jang
authors.forename: Chang-Yeol
authors.initials: CY
authors.lastname: Yim
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control*; D006648:Histocompatibility; D006801:Humans; D016130:Immunophenotyping; D007519:Isoantigens / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D016131:Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists*; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D007519:Isoantigens; D008565:Membrane Proteins; D016328:NF-kappa B; D047495:PPAR gamma; D018040:Receptors, Neurokinin-1; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D051057:Proto-Oncogene Proteins c-akt; C446603:TPTE protein, human; D051059:PTEN Phosphohydrolase