Details

Autor(en) / Beteiligte

• Cui, Ye
• Lv, Zhe
• Yang, Zeran
• Lei, Jianfeng

Titel

Inhibition of Prostaglandin-Degrading Enzyme 15-PGDH Mitigates Acute Murine Lung Allograft Rejection

Ist Teil von

• Lung, 2023-12, Vol.201 (6), p.591-601

Ort / Verlag

New York: Springer US

Erscheinungsjahr

2023

Quelle

springer (창간호~2014)

Beschreibungen/Notizen

• Purpose Acute rejection is a frequent complication among lung transplant recipients and poses substantial therapeutic challenges. 15-hydroxyprostaglandin dehydrogenase (15-PGDH), an enzyme responsible for the inactivation of prostaglandin E2 (PGE2), has recently been implicated in inflammatory lung diseases. However, the role of 15-PGDH in lung transplantation rejection remains elusive. The present study was undertaken to examine the expression of 15-PGDH in rejected lung allografts and whether inhibition of 15-PGDH ameliorates acute lung allograft rejection. Methods Orthotopic mouse lung transplantations were performed between donor and recipient mice of the same strain or allogeneic mismatched pairs. The expression of 15-PGDH in mouse lung grafts was measured. The efficacy of a selective 15-PGDH inhibitor (SW033291) in ameliorating acute rejection was assessed through histopathological examination, micro-CT imaging, and pulmonary function tests. Additionally, the mechanism underlying the effects of SW033291 treatment was explored using CD8 + T cells isolated from mouse lung allografts. Results Increased 15-PGDH expression was observed in rejected allografts and allogeneic CD8 + T cells. Treatment with SW033291 led to an accumulation of PGE2, modulation of CD8 + T-cell responses and mitochondrial activity, and improved allograft function and survival. Conclusion Our study provides new insights into the role of 15-PGDH in acute lung rejection and highlights the therapeutic potential of inhibiting 15-PGDH for enhancing graft survival. The accumulation of PGE2 and modulation of CD8 + T-cell responses represent potential mechanisms underlying the benefits of 15-PGDH inhibition in this model. Our findings provide impetus for further exploring 15-PGDH as a target for improving lung transplantation outcomes.