Dexamethasone palmitate ameliorates macrophages-rich graft-versus-host disease by inhibiting macrophage functions.
Macrophage infiltration of skin GVHD lesions correlates directly with disease severity, but the mechanisms underlying this relationship remain unclear and GVHD with many macrophages is a therapeutic challenge. Here, we characterize the macrophages involved in GVHD and report that dexamethasone palmi...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4012982?pdf=render |
| _version_ | 1811232650879303680 |
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| author | Satoshi Nishiwaki Takayuki Nakayama Makoto Murata Tetsuya Nishida Seitaro Terakura Shigeki Saito Tomonori Kato Hiroki Mizuno Nobuhiko Imahashi Aika Seto Yukiyasu Ozawa Koichi Miyamura Masafumi Ito Kyosuke Takeshita Hidefumi Kato Shinya Toyokuni Keisuke Nagao Ryuzo Ueda Tomoki Naoe |
| author_facet | Satoshi Nishiwaki Takayuki Nakayama Makoto Murata Tetsuya Nishida Seitaro Terakura Shigeki Saito Tomonori Kato Hiroki Mizuno Nobuhiko Imahashi Aika Seto Yukiyasu Ozawa Koichi Miyamura Masafumi Ito Kyosuke Takeshita Hidefumi Kato Shinya Toyokuni Keisuke Nagao Ryuzo Ueda Tomoki Naoe |
| author_sort | Satoshi Nishiwaki |
| collection | DOAJ |
| description | Macrophage infiltration of skin GVHD lesions correlates directly with disease severity, but the mechanisms underlying this relationship remain unclear and GVHD with many macrophages is a therapeutic challenge. Here, we characterize the macrophages involved in GVHD and report that dexamethasone palmitate (DP), a liposteroid, can ameliorate such GVHD by inhibiting macrophage functions. We found that host-derived macrophages could exacerbate GVHD in a mouse model through expression of higher levels of pro-inflammatory TNF-α and IFN-γ, and lower levels of anti-inflammatory IL-10 than resident macrophages in mice without GVHD. DP significantly decreased the viability and migration capacity of primary mouse macrophages compared to conventional dexamethasone in vitro. DP treatment on day 7 and day 14 decreased macrophage number, and attenuated GVHD score and subsequent mortality in a murine model. This is the first study to provide evidence that therapy for GVHD should be changed on the basis of infiltrating cell type. |
| first_indexed | 2024-04-12T11:06:37Z |
| format | Article |
| id | doaj.art-468b77c852fb4228939587485914f9c9 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T11:06:37Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-468b77c852fb4228939587485914f9c92022-12-22T03:35:43ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0195e9625210.1371/journal.pone.0096252Dexamethasone palmitate ameliorates macrophages-rich graft-versus-host disease by inhibiting macrophage functions.Satoshi NishiwakiTakayuki NakayamaMakoto MurataTetsuya NishidaSeitaro TerakuraShigeki SaitoTomonori KatoHiroki MizunoNobuhiko ImahashiAika SetoYukiyasu OzawaKoichi MiyamuraMasafumi ItoKyosuke TakeshitaHidefumi KatoShinya ToyokuniKeisuke NagaoRyuzo UedaTomoki NaoeMacrophage infiltration of skin GVHD lesions correlates directly with disease severity, but the mechanisms underlying this relationship remain unclear and GVHD with many macrophages is a therapeutic challenge. Here, we characterize the macrophages involved in GVHD and report that dexamethasone palmitate (DP), a liposteroid, can ameliorate such GVHD by inhibiting macrophage functions. We found that host-derived macrophages could exacerbate GVHD in a mouse model through expression of higher levels of pro-inflammatory TNF-α and IFN-γ, and lower levels of anti-inflammatory IL-10 than resident macrophages in mice without GVHD. DP significantly decreased the viability and migration capacity of primary mouse macrophages compared to conventional dexamethasone in vitro. DP treatment on day 7 and day 14 decreased macrophage number, and attenuated GVHD score and subsequent mortality in a murine model. This is the first study to provide evidence that therapy for GVHD should be changed on the basis of infiltrating cell type.http://europepmc.org/articles/PMC4012982?pdf=render |
| spellingShingle | Satoshi Nishiwaki Takayuki Nakayama Makoto Murata Tetsuya Nishida Seitaro Terakura Shigeki Saito Tomonori Kato Hiroki Mizuno Nobuhiko Imahashi Aika Seto Yukiyasu Ozawa Koichi Miyamura Masafumi Ito Kyosuke Takeshita Hidefumi Kato Shinya Toyokuni Keisuke Nagao Ryuzo Ueda Tomoki Naoe Dexamethasone palmitate ameliorates macrophages-rich graft-versus-host disease by inhibiting macrophage functions. PLoS ONE |
| title | Dexamethasone palmitate ameliorates macrophages-rich graft-versus-host disease by inhibiting macrophage functions. |
| title_full | Dexamethasone palmitate ameliorates macrophages-rich graft-versus-host disease by inhibiting macrophage functions. |
| title_fullStr | Dexamethasone palmitate ameliorates macrophages-rich graft-versus-host disease by inhibiting macrophage functions. |
| title_full_unstemmed | Dexamethasone palmitate ameliorates macrophages-rich graft-versus-host disease by inhibiting macrophage functions. |
| title_short | Dexamethasone palmitate ameliorates macrophages-rich graft-versus-host disease by inhibiting macrophage functions. |
| title_sort | dexamethasone palmitate ameliorates macrophages rich graft versus host disease by inhibiting macrophage functions |
| url | http://europepmc.org/articles/PMC4012982?pdf=render |
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