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

Autor: Cui Y; Department of Immunology, School of Basic Medical Sciences, Capital Medical University, #10 Xi Tou Tiao, You An Men Wai, Fengtai, Beijing, 100069, People's Republic of China. yecui@outlook.com., Lv Z; Department of Immunology, School of Basic Medical Sciences, Capital Medical University, #10 Xi Tou Tiao, You An Men Wai, Fengtai, Beijing, 100069, People's Republic of China., Yang Z; Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People's Republic of China., Lei J; Research Core Facilities, Capital Medical University, Beijing, 100069, People's Republic of China.
Jazyk: angličtina
Zdroj: Lung [Lung] 2023 Dec; Vol. 201 (6), pp. 591-601. Date of Electronic Publication: 2023 Nov 07.
DOI: 10.1007/s00408-023-00651-5
Abstrakt: 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.
(© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
Externí odkaz: