Decreased cyclooxygenase-2 associated with impaired megakaryopoiesis and thrombopoiesis in primary immune thrombocytopenia

作者：Xibing Zhuang, Pengcheng Xu, Yang Ou, Xia Shao, Ying Li, Yanna Ma, Shanshan Qin, Fanli Hua, Yanxia Zhan, Lili Ji, Tiankui Qiao, Hao Chen, Yunfeng Cheng · 发表于：Journal of Translational Medicine · 年份：2023 · DOI：10.1186/s12967-023-04389-9 · 被引用次数：5 · 研究领域：Platelet Disorders and Treatments、Inflammatory mediators and NSAID effects、Antiplatelet Therapy and Cardiovascular Diseases

BACKGROUND: Cyclooxygenase (COX)-2 is a rate-limiting enzyme in the biosynthesis of prostanoids, which is mostly inducible by inflammatory cytokines. The participation of COX-2 in the maturation of megakaryocytes has been reported but barely studied in primary immune thrombocytopenia (ITP). METHODS: The expressions of COX-2 and Caspase-1, Caspase-3 and Caspase-3 p17 subunit in platelets from ITP patients and healthy controls (HC), and the expressions of COX-2 and CD41 in bone marrow (BM) of ITP patients were measured and analyzed for correlations. The effects of COX-2 inhibitor on megakaryopoiesis and thrombopoiesis were assessed by in vitro culture of Meg01 cells and murine BM-derived megakaryocytes and in vivo experiments of passive ITP mice. RESULTS: The expression of COX-2 was decreased and Caspase-1 and Caspase-3 p17 were increased in platelets from ITP patients compared to HC. In platelets from ITP patients, the COX-2 expression was positively correlated with platelet count and negatively correlated to the expression of Caspase-1. In ITP patients BM, the expression of CD41 was positively correlated with the expression of COX-2. COX-2 inhibitor inhibited the count of megakaryocytes and impaired the maturation and platelet production in Meg01 cells and bone marrow-derived megakaryocytes. COX-2 inhibitor aggravated thrombocytopenia and damaged megakaryopoiesis in ITP murine model. CONCLUSION: COX-2 plays a vital role in the physiologic and pathologic conditions of ITP by i...