2005年7月
Involvement of prostaglandin receptors (EPR2-4) in in vivo immunosuppression of PGE2 in rat skin transplant model
INTERNATIONAL IMMUNOPHARMACOLOGY
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- 巻
- 5
- 号
- 7-8
- 開始ページ
- 1131
- 終了ページ
- 1139
- 記述言語
- 英語
- 掲載種別
- DOI
- 10.1016/j.intimp.2005.01.014
- 出版者・発行元
- ELSEVIER SCIENCE BV
Background: Prostaglandin E2 (PGE2) is known to modulate immune responses and is widely viewed as a general immunosuppressant. There have been recognized four receptors for PGE2 (EP1-EP4 receptor) so far, and EP2 and EN receptors are mainly involved in the immunosuppressive effect of PGE2 in vitro. In the present study we examined the in vivo immuno suppressive effects of selective EP receptor agonists using a high-responder rat skin transplantation model.
Materials and methods: Skin allografts from ACI donors were transplanted onto LEW recipients. Agents were injected everyday between day 0 and day 5 after skin transplantation at the dose of 300 mu g/kg subcutaneously. Survival of the skin allograft, histological changes and changes of the intragraft cytokine expressions were analyzed using the reverse transcription polymerase chain reaction (RT-PCR). We also assessed the mixed lymphocyte reaction (MLR) assay using splenocytes.
Results: PGE2 significantly prolonged allograft survival (18.8 +/- 1.5 days) compared with untreated control (14.8 +/- 0.8 days). EP2R+EP3R+EP4R agonists also prolonged allograft survival (18.0 +/- 1.0 days) although EP3R agonist or EP2R+EP4R agonists alone failed (15.5 +/- 0.7, 15.4 +/- 1.3 days, respectively). RT-PCR analysis in the skin grafts demonstrated IL-10 upregulation and IFN-gamma down-regulation in all groups except untreated control and EP2R agonist-treated groups. MLR was significantly reduced in groups of EP2R+EP4R agonists, EP2R+EP3R+EP4R agonists and PGE2, compared with untreated control.
Conclusions: The effect of PGE2 to prolong the survival of skin transplant requires the action of a combination of three receptors, i.e., EP2+EP3+EP4. (C) 2005 Elsevier B.V. All rights reserved.
Materials and methods: Skin allografts from ACI donors were transplanted onto LEW recipients. Agents were injected everyday between day 0 and day 5 after skin transplantation at the dose of 300 mu g/kg subcutaneously. Survival of the skin allograft, histological changes and changes of the intragraft cytokine expressions were analyzed using the reverse transcription polymerase chain reaction (RT-PCR). We also assessed the mixed lymphocyte reaction (MLR) assay using splenocytes.
Results: PGE2 significantly prolonged allograft survival (18.8 +/- 1.5 days) compared with untreated control (14.8 +/- 0.8 days). EP2R+EP3R+EP4R agonists also prolonged allograft survival (18.0 +/- 1.0 days) although EP3R agonist or EP2R+EP4R agonists alone failed (15.5 +/- 0.7, 15.4 +/- 1.3 days, respectively). RT-PCR analysis in the skin grafts demonstrated IL-10 upregulation and IFN-gamma down-regulation in all groups except untreated control and EP2R agonist-treated groups. MLR was significantly reduced in groups of EP2R+EP4R agonists, EP2R+EP3R+EP4R agonists and PGE2, compared with untreated control.
Conclusions: The effect of PGE2 to prolong the survival of skin transplant requires the action of a combination of three receptors, i.e., EP2+EP3+EP4. (C) 2005 Elsevier B.V. All rights reserved.
- リンク情報
- ID情報
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- DOI : 10.1016/j.intimp.2005.01.014
- ISSN : 1567-5769
- Web of Science ID : WOS:000229714300003