PPARalpha ligand WY14643 reduced acute rejection after rat lung transplantation with the upregulation of IL-4, IL-10 and TGFbeta mRNA expression
| Autor: | Takayuki Shirakusa, Takeshi Shiraishi, Masahide Kuroki, Jun Yanagisawa, Shinichi Maekawa, Hirotomo Shibaguchi, Masafumi Hiratuka, Takao Higuchi, Akinori Iwasaki, Toshihiro Tanaka |
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| Rok vydání: | 2008 |
| Předmět: |
Pulmonary and Respiratory Medicine
Graft Rejection medicine.medical_treatment Downregulation and upregulation Transforming Growth Factor beta Rats Inbred BN medicine Lung transplantation Animals PPAR alpha RNA Messenger Interleukin 4 Transplantation business.industry Interleukin Rats Inbred F344 Interleukin-10 Rats Up-Regulation Interleukin 10 surgical procedures operative Cytokine Pyrimidines Immunology Cancer research Surgery Interleukin-4 Cardiology and Cardiovascular Medicine business Transforming growth factor Lung Transplantation |
| Zdroj: | The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation. 28(11) |
| ISSN: | 1557-3117 |
| Popis: | Background The peroxisome proliferators-activated receptor-α (PPARα) is important in lipid metabolism and regulation of inflammation. Recent studies have demonstrated the immunoregulatory effects of PPARα. This investigated the immunosuppressive effects of PPARα using its ligand, WY14643, on acute lung allograft rejection in a rat model and its mechanism of action. Method The left lungs were transplanted orthotopically from Brown-Norway donors to F344 recipients. The recipients were then divided into control and WY14643 treatment groups. The allograft rejection was evaluated by daily chest X-ray imaging and was evaluated histologically on Day 7 after transplantation. The cytokine messenger RNA (mRNA) expression at Days 3 and 5 were also evaluated in allografts and recipient spleens. Results The radiologic and histologic findings indicated that treatment with the WY14643 reduced acute allograft rejection. WY14643 also significantly extended the allograft survival time. This amelioration of acute rejection by WY14643 was also associated with up-regulated interleukin (IL)-4, IL-10, and transforming growth factor-β (TGFβ) mRNA expression in the lung allografts and spleens. Conclusion This study demonstrated that the administration of the PPARa ligand, WY14643, ameliorates acute lung allograft rejection in rats. Treatment with WY14643 reduced histopathologic scores, prolonged graft survival, and up-regulated the expression of anti-inflammatory cytokine IL-4, IL-10, and TGFβ mRNA compared with the control. |
| Databáze: | OpenAIRE |
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